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Chester A Mathis - One of the best experts on this subject based on the ideXlab platform.
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Genome-wide association study of Brain amyloid deposition as measured By <B>PittsBurghB> <B>CompoundB>-B (PiB)-PET imaging
Molecular psychiatry, 2018Co-Authors: Qi Yan, Chester A Mathis, Kwangsik Nho, Jorge L. Del-aguila, Xingbin Wang, Shannon L. Risacher, Kang-hsien Fan, Beth E. Snitz, Howard J. Aizenstein, Oscar L. LopezAbstract:Deposition of amyloid plaques in the Brain is one of the two main pathological hallmarks of Alzheimer’s disease (AD). Amyloid positron emission tomography (PET) is a neuroimaging tool that selectively detects in vivo amyloid deposition in the Brain and is a reliaBle endophenotype for AD that complements cereBrospinal fluid Biomarkers with regional information. We measured in vivo amyloid deposition in the Brains of ~1000 suBjects from three collaBorative AD centers and ADNI using 11C-laBeled <B>PittsBurghB> <B>CompoundB>-B (PiB)-PET imaging followed By meta-analysis of genome-wide association studies, first to our knowledge for PiB-PET, to identify novel genetic loci for this endophenotype. The APOE region showed the most significant association where several SNPs surpassed the genome-wide significant threshold, with APOE*4 Being most significant (P-meta = 9.09E-30; β = 0.18). Interestingly, after conditioning on APOE*4, 14 SNPs remained significant at P
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genome wide association study of Brain amyloid deposition as measured By <B>PittsBurghB> <B>CompoundB> B piB pet imaging
Molecular Psychiatry, 2018Co-Authors: Qi Yan, Chester A Mathis, Kwangsik Nho, Xingbin Wang, Shannon L. Risacher, Kang-hsien Fan, Beth E. Snitz, Howard J. Aizenstein, Jorge L Delaguila, Oscar L. LopezAbstract:Deposition of amyloid plaques in the Brain is one of the two main pathological hallmarks of Alzheimer’s disease (AD). Amyloid positron emission tomography (PET) is a neuroimaging tool that selectively detects in vivo amyloid deposition in the Brain and is a reliaBle endophenotype for AD that complements cereBrospinal fluid Biomarkers with regional information. We measured in vivo amyloid deposition in the Brains of ~1000 suBjects from three collaBorative AD centers and ADNI using 11C-laBeled <B>PittsBurghB> <B>CompoundB>-B (PiB)-PET imaging followed By meta-analysis of genome-wide association studies, first to our knowledge for PiB-PET, to identify novel genetic loci for this endophenotype. The APOE region showed the most significant association where several SNPs surpassed the genome-wide significant threshold, with APOE*4 Being most significant (P-meta = 9.09E-30; β = 0.18). Interestingly, after conditioning on APOE*4, 14 SNPs remained significant at P < 0.05 in the APOE region that were not in linkage disequiliBrium with APOE*4. Outside the APOE region, the meta-analysis revealed 15 non-APOE loci with P < 1E-05 on nine chromosomes, with two most significant SNPs on chromosomes 8 (P-meta = 4.87E-07) and 3 (P-meta = 9.69E-07). Functional analyses of these SNPs indicate their potential relevance with AD pathogenesis. Top 15 non-APOE SNPs along with APOE*4 explained 25–35% of the amyloid variance in different datasets, of which 14–17% was explained By APOE*4 alone. In conclusion, we have identified novel signals in APOE and non-APOE regions that affect amyloid deposition in the Brain. Our data also highlights the presence of yet to Be discovered variants that may Be responsiBle for the unexplained genetic variance of amyloid deposition.
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amyloid β imaging with <B>PittsBurghB> <B>CompoundB> B and florBetapir comparing radiotracers and quantification methods
The Journal of Nuclear Medicine, 2013Co-Authors: Chester A Mathis, Michael J Pontecorvo, Susan M Landau, Christopher Breault, Abhinay D Joshi, William J JagustAbstract:Pet of fiBrillar amyloid-β (Aβ) in vivo has had a suBstantial impact on Alzheimer disease (AD) research. The first selective radioligand developed for this purpose, 11C-<B>PittsBurghB> <B>CompoundB> B (PiB), has played a critical role in this research, contriButing to the increasing understanding of disease development and the presence of cortical Aβ in the cognitively normal older population. Because the 20-min half-life of 11C-laBeled radioligands such as PiB restricts their use to centers with a cyclotron on-site, the recent development of 18F-laBeled radioligands such as florBetapir promises to facilitate the accessiBility of Aβ imaging in AD research. The longer half-life of 18F (110 min) makes it possiBle to transport these radioligands from production site to PET scanner. Validation studies have estaBlished that cortical Aβ measured with florBetapir can Be detected in cognitively normal suBjects, in patients with mild cognitive impairment (MCI), and in patients with Alzheimer disease (AD) (1,2) in proportions comparaBle to those reported for PiB (3). Furthermore, autopsy studies in which individuals were scanned with PiB (4) and florBetapir (5,6) Before death have provided additional evidence that Both PET ligands Bind to fiBrillar amyloid in cortex. However, data directly comparing PiB and florBetapir in the same individuals are still limited (7). The goal of this study was to compare measurements of cortical retention ratios of PiB and florBetapir in a suBset of Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants who underwent 2 consecutive PiB imaging sessions followed By 1 florBetapir scanning session at approximately 1- to 2-y intervals. Because the precise quantification of cortical Aβ may Be influenced By various image processing and analysis methods, we examined the influence of several of these factors. Finally, we examined the feasiBility of transforming cutoff thresholds for Aβ positivity, with the goal of working toward standardization in Aβ imaging quantification.
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imaging Brain amyloid in nondemented young adults with down syndrome using <B>PittsBurghB> <B>CompoundB> B
Alzheimers & Dementia, 2012Co-Authors: Benjamin L Handen, Chester A Mathis, Julie C Price, Ann D Cohen, Umapathy Channamalappa, Peter Bulova, Sheila Cannon, William I Cohen, William E KlunkAbstract:ABstract Down syndrome (DS) is one of the most common causes of intellectual disaBility. Although DS accounts for only 15% of all individuals with intellectual disaBilities, adults with DS account for approximately 60% of individuals with intellectual disaBilities and Alzheimer's disease. This is thought to Be Because of overproduction of the β-amyloid (Aβ) protein due to trisomy for the Aβ precursor protein gene on chromosome 21. <B>PittsBurghB> <B>CompoundB> B (PiB) is a noninvasive in vivo positron emission tomography tracer used to image amyloid deposition in living humans. Studies using PiB have shown an age-dependent asymptomatic amyloid deposition in more than 20% of the cognitively normal elderly population. Presymptomatic carriers of presenilin (PS-1) and Aβ precursor protein gene mutations who are destined to develop Alzheimer's disease also show preclinical amyloid deposition. This report descriBes a pilot study involving the use of PiB in seven adults with DS (age: 20–44 years). Compared with oBjective cutoffs for amyloid positivity in older non-DS cognitively normal control suBjects, only two of the seven DS suBjects (age: 38 and 44 years) showed increased PiB retention. The remaining five suBjects aged Between 20 and 35 years showed no detectaBle increase in PiB retention. Interestingly, the two suBjects who showed elevated PiB retention showed a striatal-predominant pattern similar to that previously reported for PS-1 mutation carriers. These results demonstrate the feasiBility of conducting PiB positron emission tomography scanning in this special population, and suggest a link Between Aβ overproduction and early striatal deposition of fiBrillar Aβ.
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Characterizing regional correlation, laterality and symmetry of amyloid deposition in mild cognitive impairment and Alzheimer's disease with <B>PittsBurghB> <B>CompoundB> B
Journal of neuroscience methods, 2008Co-Authors: Cyrus A. Raji, Chester A Mathis, Julie C Price, Brian J Lopresti, Jessica A Hoge, Scott K Ziolko, Nicholas D. Tsopelas, James T. Becker, Judith Saxton, Steven T DekoskyAbstract:ABstract We evaluated the region-to-region correlation, laterality and asymmetry of amyloid deposition in suBjects with mild cognitive impairment (MCI) or Alzheimer's disease (AD) using the amyloid tracer, <B>PittsBurghB> <B>CompoundB> B (PiB). Seventeen suBjects, including 7 with MCI (MMSE 26.7 ± 2.4) and 10 with AD (MMSE of 24.8 ± 2.7) underwent PiB imaging. Measures of laterality (i.e., group-wise predilection for right or left) and asymmetry (i.e., group-wise predilection for unequal PiB retention Between the two hemispheres) were calculated for 17 Regions of Interest (ROIs). Regional correlations were calculated along with within-group and Between-groups statistical analyses of laterality and asymmetry metrics. The median correlation Between PiB retention across all pairs of ROIs was 0.65, with highest correlations found in areas of highest PiB retention (r = 0.74). Overall, PiB retention was symmetric Bilaterally, But there was PiB laterality in MCI in dorsal frontal cortex [(t(6) = 3.05, p = 0.02, L > R] and sensory-motor area [t(6) = 3.10, p = 0.02, L > R] and in AD in the occipital pole (t(9) = −2.63, p = 0.03, R > L). The most significant asymmetries in PiB retention were found in suB-cortical white matter (t(6) = 3.99, p = 0.01) and middle precuneus [(t(6) = 3.57, p = 0.01] in MCI, and in lateral temporal cortex (t(9) = 3.02, p = 0.01) and anterior ventral striatum [t(9) = 2.37, p = 0.04] in AD. No group differences (AD versus MCI) were detected in laterality [F (1, 15) = 0.15, p = 0.7] or asymmetry [F (1, 15) = 0.7, p = 0.42].
William E Klunk - One of the best experts on this subject based on the ideXlab platform.
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comparison of <B>PittsBurghB> <B>CompoundB> B and florBetapir in cross sectional and longitudinal studies
Alzheimer's & Dementia: Diagnosis Assessment & Disease Monitoring, 2019Co-Authors: Shaney Flores, William E Klunk, Guoqiao Wang, Russ C Hornbeck, Benjamin Speidel, Nelly Josephmathurin, Andrei G Vlassenko, Brian A Gordon, Robert A Koeppe, Clifford R JackAbstract:ABstract Introduction Quantitative in vivo measurement of Brain amyloid Burden is important for Both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of <B>PittsBurghB> <B>CompoundB> B–Based and florBetapir-Based amyloid imaging in the same participants from two independent cohorts using a crossover design. Methods <B>PittsBurghB> <B>CompoundB> B and florBetapir amyloid PET imaging data from three different cohorts were analyzed using previously estaBlished pipelines to oBtain gloBal amyloid Burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison Between the two tracers. The mean and inter-individual variaBility of the two tracers were compared using multivariate linear models Both cross-sectionally and longitudinally. Results GloBal amyloid Burden measured using the two tracers were strongly correlated in Both cohorts. However, higher variaBility was oBserved when florBetapir was used as the imaging tracer. The variaBility may Be partially caused By white matter signal as partial volume correction reduces the variaBility and improves the correlations Between the two tracers. Amyloid Burden measured using Both tracers was found to Be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar But separate cohorts whose Baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers. Discussion Although the amyloid Burden measurements were quite similar using these two tracers as expected, difference was oBservaBle even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers.
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Quantitative PET and Histology of Brain Biopsy Reveal Lack of Selective <B>PittsBurghB> <B>CompoundB>-B Binding to IntracereBral Amyloidoma.
Journal of Alzheimer's disease : JAD, 2018Co-Authors: Colin Groot, William E Klunk, Nelleke Tolboom, Milos D Ikonomovic, Adriaan A. Lammertsma, Baayla D.c. Boon, Frederik Barkhof, Philip Scheltens, Annemieke J.m. Rozemuller, Rik OssenkoppeleAbstract:This single case study examines selective <B>PittsBurghB> <B>CompoundB>-B (PiB) Binding to an intracereBral light-chain amyloidoma using a 90-minute dynamic [11C]PiB-PET scan and Brain Biopsy tissue. Parametric non-displaceaBle Binding potential (BPND) images showed low specific Binding in the amyloidoma (BPND = 0.23), while relative tracer delivery was adequate (R1 = 0.44). Histology of the tissue revealed strong coloring with Congo-red, thioflavin-S, and X-34, indicating presence of amyloid. However, immunological staining with 6F/3D revealed aBsence of amyloid-β and histofluorescence of 6-CN-PiB, a highly fluorescent derivative of PiB, was at Background levels. Our results suggest that PiB does not detect the atypical amyloid pathology associated with an intracereBral light-chain amyloidoma. These findings are of interest to clinicians and researchers applying [11C]PiB-PET to detect atypical forms of amyloid pathology.
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the effects of normal aging on amyloid β deposition in nondemented adults with down syndrome as imaged By carBon 11 laBeled <B>PittsBurghB> <B>CompoundB> B
Alzheimers & Dementia, 2016Co-Authors: Tobey J Betthauser, William E Klunk, Julie C Price, Peter Bulova, Ansel T Hillmer, Iulia Mihaila, Andrew T Higgins, Sigan L Hartley, Regina M Hardison, Rameshwari V TumuluruAbstract:ABstract Introduction In Down syndrome (DS), the overproduction of amyloid precursor protein is hypothesized to predispose young adults to early expression of Alzheimer-like neuropathology. Methods PET imaging with carBon 11–laBeled <B>PittsBurghB> <B>CompoundB> B examined the pattern of amyloid-β deposition in 68 nondemented adults with DS (30–53 years) to determine the relationship Between deposition and normal aging. Standard uptake value ratio (SUVR) images were created with cereBellar gray matter as the reference region. Results Multiple linear regression revealed slight But highly significant (corrected P Conclusion There is an age-related amyloid-β deposition in the DS population, But as a pattern of elevated cortical retention Becomes apparent, the correlation of SUVR with age ceases to Be significant. Factors unrelated to aging may drive an increase in deposition during early Alzheimer's disease pathogenesis.
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Reduced Binding of <B>PittsBurghB> <B>CompoundB>-B in areas of white matter hyperintensities.
NeuroImage. Clinical, 2015Co-Authors: A.e. Goodheart, Julie C Price, Beth E. Snitz, Howard J. Aizenstein, Oscar L. Lopez, Erica Tamburo, Davneet S. Minhas, Eric Mcdade, Chet Mathis, William E KlunkAbstract:The amyloid imaging agent, <B>PittsBurghB> <B>CompoundB>-B, Binds with high affinity to β-amyloid (Aβ) in the Brain, and it is well estaBlished that PiB also shows non-specific retention in white matter (WM). However, little is known aBout retention of PiB in areas of white matter hyperintensities (WMH), aBnormalities commonly seen in older adults. Further, it is hypothesized that WMH are related to Both cognitive dysfunction and Aβ deposition. The goal of the present study was to explore PiB retention in Both normal-appearing WM (NAWM) and WMH in a group of elderly, cognitively normal individuals. In a group of cognitively normal elderly (n = 64; 86.5 ± 2.6 years) two analyses were applied: (1) ROIs were placed over periventricular areas in which WMH caps are commonly seen on all suBjects, regardless of WMH Burden or size. (2) SuBject-specific maps of NAWM and WMH were co-registered with the PiB-PET images and mean SUVR values were calculated in these NAWM and WMH maps. PiB retention was significantly reduced in the ROIs of suBjects with high WMH compared to suBjects with low WMH. Additionally, in suBjects with high WMH, there was significantly lower PiB retention in suBject-specific maps of WMH compared to NAWM, which was not oBserved in suBjects with low WMH, likely Because of the small size of WMH maps in this group. These data suggest that WM in areas of WMH Binds PiB less effectively than does normal WM. Further exploration of this phenomenon may lead to insights aBout the molecular Basis of the non-specific retention of amyloid tracers in white matter.
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The effects of normal aging on amyloid-β deposition in nondemented adults with Down syndrome as imaged By carBon 11–laBeled <B>PittsBurghB> <B>CompoundB> B
Alzheimer's & dementia : the journal of the Alzheimer's Association, 2015Co-Authors: Patrick J. Lao, William E Klunk, Julie C Price, Peter Bulova, Tobey J Betthauser, Ansel T Hillmer, Iulia Mihaila, Andrew T Higgins, Sigan L Hartley, Regina M HardisonAbstract:ABstract Introduction In Down syndrome (DS), the overproduction of amyloid precursor protein is hypothesized to predispose young adults to early expression of Alzheimer-like neuropathology. Methods PET imaging with carBon 11–laBeled <B>PittsBurghB> <B>CompoundB> B examined the pattern of amyloid-β deposition in 68 nondemented adults with DS (30–53 years) to determine the relationship Between deposition and normal aging. Standard uptake value ratio (SUVR) images were created with cereBellar gray matter as the reference region. Results Multiple linear regression revealed slight But highly significant (corrected P Conclusion There is an age-related amyloid-β deposition in the DS population, But as a pattern of elevated cortical retention Becomes apparent, the correlation of SUVR with age ceases to Be significant. Factors unrelated to aging may drive an increase in deposition during early Alzheimer's disease pathogenesis.
Steven T Dekosky - One of the best experts on this subject based on the ideXlab platform.
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consideration of optimal time window for <B>PittsBurghB> <B>CompoundB> B pet summed uptake measurements
The Journal of Nuclear Medicine, 2009Co-Authors: R L Mcnamee, William E Klunk, Julie C Price, Brian J Lopresti, Scott K Ziolko, Seonghwan Yee, Bedda L Rosario, Lisa A Weissfeld, Michael Berginc, Steven T DekoskyAbstract:<B>PittsBurghB> <B>CompoundB> B (PiB) is a 11C-laBeled thioflavin-T derivative that has Become widely used (1–3) in imaging amyloid-β–protein deposits with PET. Amyloid imaging has proven to Be useful in the study of Alzheimer disease (AD) (4–11). In the proof-of-concept human studies (4), PiB retention was assessed using the semiquantitative standardized uptake value ratio (SUVR; summed tissue uptake over 40–60 min), and these results were suBsequently verified By fully quantitative studies performed in controls, patients with mild cognitive impairment (MCI), and patients with AD (5,6). These early studies consistently showed that PiB uptake in AD patients was nearly twice that in controls in specific cortical areas (P < 0.002) But similar in amyloid-spared areas (suBcortical white matter [SWM], cereBellum). PiB retention in MCI patients appeared either AD-like or control-like. Quantitative studies require dynamic sampling of the radiotracer kinetics in Brain and Blood at many times throughout the study (e.g., 30–40 points over ≥90 min), analysis of arterial plasma to determine the metaBolite-corrected arterial input function, and compartmental modeling analyses to oBtain regional Binding measurements (e.g., distriBution volume ratio [DVR] = total distriBution volume [VT]/nondisplaceaBle distriBution volume [VND]). The quantitative arterial input–Based DVR measurements generally serve as gold-standard outcomes for suBsequent evaluations directed toward the identification of valid simpler methods that do not require Blood sampling and allow for shorter data-collection times. Lopresti et al. (6) analyzed simplified PiB PET data over 60- and 90-min intervals using the linear Logan graphical analysis with different input functions that were either arterial, image-derived carotid, or image-derived cereBellar data. Data also were analyzed with a simplified reference tissue method and the summed SUVR. Although results oBtained using data over the full 90-min scan interval were less variaBle than were data over the shorter 60-min interval, the 60-min data provided useful results. Of all compared methods, the SUVR approach was the most roBust in terms of test–retest variaBility and maximum effect size Between AD patients and controls, although the SUVR method required the shortest scan time (e.g., 40–60 min or 40–90 min). The SUVR is easy to compute, requires no arterial input function, and produces data with a large dynamic range, thereBy making it a potential candidate for routine clinical studies (6). SUVR can also serve as an approximation of DVR, although Bias (overestimation relative to the true DVR) can arise as a result of plasma clearance (12). The present work examined the PiB SUVR to determine an optimal short time window for the SUVR data collection across the control, MCI, and AD groups. A systematic evaluation was performed for several 20- and 30-min SUVR time windows, as these are the most feasiBle for routine clinical settings. This evaluation considered several factors, including correlation of the SUVR to Logan DVR (arterial and cereBellar input), the effective contrast of the SUVR for AD versus control groups, and the temporal dynamics of the theoretic SUVR curve.
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Characterizing regional correlation, laterality and symmetry of amyloid deposition in mild cognitive impairment and Alzheimer's disease with <B>PittsBurghB> <B>CompoundB> B
Journal of neuroscience methods, 2008Co-Authors: Cyrus A. Raji, Chester A Mathis, Julie C Price, Brian J Lopresti, Jessica A Hoge, Scott K Ziolko, Nicholas D. Tsopelas, James T. Becker, Judith Saxton, Steven T DekoskyAbstract:ABstract We evaluated the region-to-region correlation, laterality and asymmetry of amyloid deposition in suBjects with mild cognitive impairment (MCI) or Alzheimer's disease (AD) using the amyloid tracer, <B>PittsBurghB> <B>CompoundB> B (PiB). Seventeen suBjects, including 7 with MCI (MMSE 26.7 ± 2.4) and 10 with AD (MMSE of 24.8 ± 2.7) underwent PiB imaging. Measures of laterality (i.e., group-wise predilection for right or left) and asymmetry (i.e., group-wise predilection for unequal PiB retention Between the two hemispheres) were calculated for 17 Regions of Interest (ROIs). Regional correlations were calculated along with within-group and Between-groups statistical analyses of laterality and asymmetry metrics. The median correlation Between PiB retention across all pairs of ROIs was 0.65, with highest correlations found in areas of highest PiB retention (r = 0.74). Overall, PiB retention was symmetric Bilaterally, But there was PiB laterality in MCI in dorsal frontal cortex [(t(6) = 3.05, p = 0.02, L > R] and sensory-motor area [t(6) = 3.10, p = 0.02, L > R] and in AD in the occipital pole (t(9) = −2.63, p = 0.03, R > L). The most significant asymmetries in PiB retention were found in suB-cortical white matter (t(6) = 3.99, p = 0.01) and middle precuneus [(t(6) = 3.57, p = 0.01] in MCI, and in lateral temporal cortex (t(9) = 3.02, p = 0.01) and anterior ventral striatum [t(9) = 2.37, p = 0.04] in AD. No group differences (AD versus MCI) were detected in laterality [F (1, 15) = 0.15, p = 0.7] or asymmetry [F (1, 15) = 0.7, p = 0.42].
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Imaging Alzheimer Pathology in Late-Life Depression With PET and <B>PittsBurghB> <B>CompoundB>-B
Alzheimer disease and associated disorders, 2008Co-Authors: Meryl A. Butters, William E Klunk, Chester A Mathis, Julie C Price, Brian J Lopresti, Jessica A Hoge, Scott K Ziolko, Nicholas D. Tsopelas, Charles F. Reynolds, Steven T DekoskyAbstract:There is increasing evidence for an empiric link Between late-life depression and Alzheimer disease (AD). The neuropathology of AD, previously only confirmed at autopsy, may now Be detectaBle in vivo using selective imaging ligands for β-amyloid. Positron emission tomography (PET) with [11C] 6-OH-BTA-1 [<B>PittsBurghB> <B>CompoundB>-B (PiB)] has shown high tracer retention in cortical areas in patients with clinical diagnoses of proBaBle AD and low retention in age-matched controls. We also previously reported variaBle PiB retention in patients with mild cognitive impairment (MCI). In this study, we used PiB-PET to evaluate whether amyloid is present in elders with treated major depression, many of whom have persistent cognitive impairment. We evaluated 9 suBjects with remitted major depression [3M: 6F, mean (SD) age=71.8(5.7) y]. Seven of the 9 depressed suBjects also met criteria for the diagnosis of MCI. PiB-PET data from healthy elders [n=8; mean (SD) age=71.5(3.0) y] were used for comparison. PET was acquired with arterial sampling and PiB retention was quantified using magnetic resonance imaging-guided cortical regions and graphical analysis of time-activity data; arterial line failure led to exclusion of 1 depressed suBject. The data demonstrated variaBly elevated PiB retention. PiB retention in the 2 depressed suBjects with normal cognitive aBility was in the range of nondepressed cognitively normal suBjects. PiB retention in 3 of the 6 depressed suBjects with MCI fell in the range of suBjects with AD. PiB retention in the remaining 3 depressed suBjects with cooccurring MCI was variaBle and generally was intermediate to the other suBjects. Our findings are consistent with and supportive of the hypothesis that depression may herald the development of AD in some individuals.
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molecular imaging with <B>PittsBurghB> <B>CompoundB> B confirmed at autopsy a case report
JAMA Neurology, 2007Co-Authors: Brian J Bacskai, Stefanie H Freeman, Scott B Raymond, Keith Johnson, William E Klunk, Michael C Irizarry, Matthew P. Frosch, Chester A Mathis, Jean C Augustinack, Steven T DekoskyAbstract:OBjective To determine the correspondence Between uptake of <B>PittsBurghB> <B>CompoundB> B (PiB) in life and measures of β-amyloid (Aβ) in postmortem tissue analysis. Patient A 76-year-old man with a clinical diagnosis of dementia with Lewy Bodies underwent fluorodeoxyglucose 18 F and PiB positron emission tomographic Brain scans. Imaging revealed marked region specific Binding of PiB and aBnormal fluorodeoxyglucose uptake. Intervention Autopsy was performed 3 months after the PiB scan. Results Autopsy confirmed the clinical diagnosis; in addition, there was severe cereBral amyloid angiopathy and only moderate numBers of parenchymal Aβ plaques. Biochemical measures revealed a positive correlation Between Aβ levels and regional PiB Binding. Conclusion This report confirms that PiB detects Aβ in the living patient and demonstrates that amyloid deposited as cereBral amyloid angiopathy can Be the dominant source of signal.
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simplified quantification of <B>PittsBurghB> <B>CompoundB> B amyloid imaging pet studies a comparative analysis
The Journal of Nuclear Medicine, 2005Co-Authors: Brian J Lopresti, William E Klunk, Chester A Mathis, Xueling Lu, Jessica A Hoge, Scott K Ziolko, Carolyn C Meltzer, Nicholas D. Tsopelas, Kurt Schimmel, Steven T DekoskyAbstract:PET studies have Been performed using the amyloid Binding radiotracer <B>PittsBurghB> <B>CompoundB> B (PIB). Previous quantitative analyses using arterial Blood showed that the Logan graphical analysis using 90 min of emission data(ART90) provided a reliaBle measure of PIB retention. This work reports on simplified methods of analysis for human PIB imaging. Methods: PIB PET scans were conducted in 24 suBjects (6 Alzheimer's disease [AD], 10 mild cognitive impairment [MCI], 8 controls) with arterial Blood sampling. Retest scans were performed on 8 suBjects (3 AD, 1 MCI, 4 controls) within 28 d. Data were analyzed over 60 and 90 min using the Logan analysis and (a) metaBolite-corrected input functions Based on arterial plasma (ART60, ART90), (B) carotid artery time-activity data with a population average metaBolite correction (CAR60, CAR90); and (c) cereBellar reference tissue (CER60, CER90). Data also were analyzed using the simplified reference tissue method (SRTM60, SRTM90) and a single-scan method Based on late-scan ratios of standardized uptake values (SUVR60, SUVR90). Results: All methods of analysis examined effectively discerned regional differences Between AD and control suBjects in amyloid-laden cortical regions, although the performance of the simplified methods varied in terms of Bias, test-retest variaBility, intersuBject variaBility, and effect size. CAR90 Best agreed with ART90 distriBution volume ratio (DVR) measures across Brain regions and suBject groups and demonstrated satisfactory test-retest variaBility (′7.1 % across regions). CER90 and CER60 showed negative Biases relative to ART90 in high-DVR suBjects But had the lowest test-retest variaBility. The single-scan SUV-Based methods showed the largest effect sizes for AD and control group differences and performed well in terms of intersuBject and test-retest variaBility. Conclusion: Of the simplified methods for PIB analysis examined, CAR90 provided DVR measures that were most comparaBle to ART90; CER90 was the most reproduciBle and SUVR90 produced the largest effect size. All simplified methods were effective at distinguishing AD and control differences and may Be effectively used in the analysis of PIB. SUVR60 data can Be oBtained with as little as 20 min of PET emission data collection. The relative strengths and limitations of each method must Be considered for each experimental design.
Julie C Price - One of the best experts on this subject based on the ideXlab platform.
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the effects of normal aging on amyloid β deposition in nondemented adults with down syndrome as imaged By carBon 11 laBeled <B>PittsBurghB> <B>CompoundB> B
Alzheimers & Dementia, 2016Co-Authors: Tobey J Betthauser, William E Klunk, Julie C Price, Peter Bulova, Ansel T Hillmer, Iulia Mihaila, Andrew T Higgins, Sigan L Hartley, Regina M Hardison, Rameshwari V TumuluruAbstract:ABstract Introduction In Down syndrome (DS), the overproduction of amyloid precursor protein is hypothesized to predispose young adults to early expression of Alzheimer-like neuropathology. Methods PET imaging with carBon 11–laBeled <B>PittsBurghB> <B>CompoundB> B examined the pattern of amyloid-β deposition in 68 nondemented adults with DS (30–53 years) to determine the relationship Between deposition and normal aging. Standard uptake value ratio (SUVR) images were created with cereBellar gray matter as the reference region. Results Multiple linear regression revealed slight But highly significant (corrected P Conclusion There is an age-related amyloid-β deposition in the DS population, But as a pattern of elevated cortical retention Becomes apparent, the correlation of SUVR with age ceases to Be significant. Factors unrelated to aging may drive an increase in deposition during early Alzheimer's disease pathogenesis.
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Reduced Binding of <B>PittsBurghB> <B>CompoundB>-B in areas of white matter hyperintensities.
NeuroImage. Clinical, 2015Co-Authors: A.e. Goodheart, Julie C Price, Beth E. Snitz, Howard J. Aizenstein, Oscar L. Lopez, Erica Tamburo, Davneet S. Minhas, Eric Mcdade, Chet Mathis, William E KlunkAbstract:The amyloid imaging agent, <B>PittsBurghB> <B>CompoundB>-B, Binds with high affinity to β-amyloid (Aβ) in the Brain, and it is well estaBlished that PiB also shows non-specific retention in white matter (WM). However, little is known aBout retention of PiB in areas of white matter hyperintensities (WMH), aBnormalities commonly seen in older adults. Further, it is hypothesized that WMH are related to Both cognitive dysfunction and Aβ deposition. The goal of the present study was to explore PiB retention in Both normal-appearing WM (NAWM) and WMH in a group of elderly, cognitively normal individuals. In a group of cognitively normal elderly (n = 64; 86.5 ± 2.6 years) two analyses were applied: (1) ROIs were placed over periventricular areas in which WMH caps are commonly seen on all suBjects, regardless of WMH Burden or size. (2) SuBject-specific maps of NAWM and WMH were co-registered with the PiB-PET images and mean SUVR values were calculated in these NAWM and WMH maps. PiB retention was significantly reduced in the ROIs of suBjects with high WMH compared to suBjects with low WMH. Additionally, in suBjects with high WMH, there was significantly lower PiB retention in suBject-specific maps of WMH compared to NAWM, which was not oBserved in suBjects with low WMH, likely Because of the small size of WMH maps in this group. These data suggest that WM in areas of WMH Binds PiB less effectively than does normal WM. Further exploration of this phenomenon may lead to insights aBout the molecular Basis of the non-specific retention of amyloid tracers in white matter.
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The effects of normal aging on amyloid-β deposition in nondemented adults with Down syndrome as imaged By carBon 11–laBeled <B>PittsBurghB> <B>CompoundB> B
Alzheimer's & dementia : the journal of the Alzheimer's Association, 2015Co-Authors: Patrick J. Lao, William E Klunk, Julie C Price, Peter Bulova, Tobey J Betthauser, Ansel T Hillmer, Iulia Mihaila, Andrew T Higgins, Sigan L Hartley, Regina M HardisonAbstract:ABstract Introduction In Down syndrome (DS), the overproduction of amyloid precursor protein is hypothesized to predispose young adults to early expression of Alzheimer-like neuropathology. Methods PET imaging with carBon 11–laBeled <B>PittsBurghB> <B>CompoundB> B examined the pattern of amyloid-β deposition in 68 nondemented adults with DS (30–53 years) to determine the relationship Between deposition and normal aging. Standard uptake value ratio (SUVR) images were created with cereBellar gray matter as the reference region. Results Multiple linear regression revealed slight But highly significant (corrected P Conclusion There is an age-related amyloid-β deposition in the DS population, But as a pattern of elevated cortical retention Becomes apparent, the correlation of SUVR with age ceases to Be significant. Factors unrelated to aging may drive an increase in deposition during early Alzheimer's disease pathogenesis.
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imaging Brain amyloid in nondemented young adults with down syndrome using <B>PittsBurghB> <B>CompoundB> B
Alzheimers & Dementia, 2012Co-Authors: Benjamin L Handen, Chester A Mathis, Julie C Price, Ann D Cohen, Umapathy Channamalappa, Peter Bulova, Sheila Cannon, William I Cohen, William E KlunkAbstract:ABstract Down syndrome (DS) is one of the most common causes of intellectual disaBility. Although DS accounts for only 15% of all individuals with intellectual disaBilities, adults with DS account for approximately 60% of individuals with intellectual disaBilities and Alzheimer's disease. This is thought to Be Because of overproduction of the β-amyloid (Aβ) protein due to trisomy for the Aβ precursor protein gene on chromosome 21. <B>PittsBurghB> <B>CompoundB> B (PiB) is a noninvasive in vivo positron emission tomography tracer used to image amyloid deposition in living humans. Studies using PiB have shown an age-dependent asymptomatic amyloid deposition in more than 20% of the cognitively normal elderly population. Presymptomatic carriers of presenilin (PS-1) and Aβ precursor protein gene mutations who are destined to develop Alzheimer's disease also show preclinical amyloid deposition. This report descriBes a pilot study involving the use of PiB in seven adults with DS (age: 20–44 years). Compared with oBjective cutoffs for amyloid positivity in older non-DS cognitively normal control suBjects, only two of the seven DS suBjects (age: 38 and 44 years) showed increased PiB retention. The remaining five suBjects aged Between 20 and 35 years showed no detectaBle increase in PiB retention. Interestingly, the two suBjects who showed elevated PiB retention showed a striatal-predominant pattern similar to that previously reported for PS-1 mutation carriers. These results demonstrate the feasiBility of conducting PiB positron emission tomography scanning in this special population, and suggest a link Between Aβ overproduction and early striatal deposition of fiBrillar Aβ.
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consideration of optimal time window for <B>PittsBurghB> <B>CompoundB> B pet summed uptake measurements
The Journal of Nuclear Medicine, 2009Co-Authors: R L Mcnamee, William E Klunk, Julie C Price, Brian J Lopresti, Scott K Ziolko, Seonghwan Yee, Bedda L Rosario, Lisa A Weissfeld, Michael Berginc, Steven T DekoskyAbstract:<B>PittsBurghB> <B>CompoundB> B (PiB) is a 11C-laBeled thioflavin-T derivative that has Become widely used (1–3) in imaging amyloid-β–protein deposits with PET. Amyloid imaging has proven to Be useful in the study of Alzheimer disease (AD) (4–11). In the proof-of-concept human studies (4), PiB retention was assessed using the semiquantitative standardized uptake value ratio (SUVR; summed tissue uptake over 40–60 min), and these results were suBsequently verified By fully quantitative studies performed in controls, patients with mild cognitive impairment (MCI), and patients with AD (5,6). These early studies consistently showed that PiB uptake in AD patients was nearly twice that in controls in specific cortical areas (P < 0.002) But similar in amyloid-spared areas (suBcortical white matter [SWM], cereBellum). PiB retention in MCI patients appeared either AD-like or control-like. Quantitative studies require dynamic sampling of the radiotracer kinetics in Brain and Blood at many times throughout the study (e.g., 30–40 points over ≥90 min), analysis of arterial plasma to determine the metaBolite-corrected arterial input function, and compartmental modeling analyses to oBtain regional Binding measurements (e.g., distriBution volume ratio [DVR] = total distriBution volume [VT]/nondisplaceaBle distriBution volume [VND]). The quantitative arterial input–Based DVR measurements generally serve as gold-standard outcomes for suBsequent evaluations directed toward the identification of valid simpler methods that do not require Blood sampling and allow for shorter data-collection times. Lopresti et al. (6) analyzed simplified PiB PET data over 60- and 90-min intervals using the linear Logan graphical analysis with different input functions that were either arterial, image-derived carotid, or image-derived cereBellar data. Data also were analyzed with a simplified reference tissue method and the summed SUVR. Although results oBtained using data over the full 90-min scan interval were less variaBle than were data over the shorter 60-min interval, the 60-min data provided useful results. Of all compared methods, the SUVR approach was the most roBust in terms of test–retest variaBility and maximum effect size Between AD patients and controls, although the SUVR method required the shortest scan time (e.g., 40–60 min or 40–90 min). The SUVR is easy to compute, requires no arterial input function, and produces data with a large dynamic range, thereBy making it a potential candidate for routine clinical studies (6). SUVR can also serve as an approximation of DVR, although Bias (overestimation relative to the true DVR) can arise as a result of plasma clearance (12). The present work examined the PiB SUVR to determine an optimal short time window for the SUVR data collection across the control, MCI, and AD groups. A systematic evaluation was performed for several 20- and 30-min SUVR time windows, as these are the most feasiBle for routine clinical settings. This evaluation considered several factors, including correlation of the SUVR to Logan DVR (arterial and cereBellar input), the effective contrast of the SUVR for AD versus control groups, and the temporal dynamics of the theoretic SUVR curve.
Kejal Kantarci - One of the best experts on this subject based on the ideXlab platform.
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White matter reference region in PET studies of 11C-<B>PittsBurghB> <B>CompoundB> B uptake: effects of age and amyloid-β deposition
Journal of nuclear medicine : official publication Society of Nuclear Medicine, 2018Co-Authors: Val J Lowe, Scott A Przybelski, Ronald C Petersen, Kejal Kantarci, Christopher G Schwarz, Matthew L Senjem, David S. Knopman, Emily S. Lundt, Hoon Ki Min, Clifford R JackAbstract:Amyloid-β (Aβ) deposition as seen on PET using an Aβ-Binding agent is a critical diagnostic Biomarker for Alzheimer disease (AD). Some reports suggest using white matter (WM) as a reference region for quantification of serial Aβ PET studies; however, nonspecific WM retention in Aβ PET in people with dementia or cognitively unimpaired (CU) has Been widely reported and is poorly understood. Methods: To investigate the suitaBility of WM as a reference region and the factors affecting WM 11C-<B>PittsBurghB> <B>CompoundB> B (11C-PiB) uptake variaBility, we conducted a retrospective study on 2 large datasets: a longitudinal study of participants (n = 577) who were CU, had mild cognitive impairment, or had dementia likely due to AD; and a cross-sectional study of single-scan PET imaging in CU suBjects (n = 1,349). In the longitudinal study, annual changes in WM 11C-PiB uptake were assessed, and in the cross-sectional study, WM 11C-PiB uptake was assessed relative to suBject age. Results: Overall, we found that WM 11C-PiB uptake showed age-related increases, which varied with the WM regions selected. Further, variaBle annual WM 11C-PiB uptake changes were seen with different gray matter (GM) 11C-PiB Baseline uptake levels. Conclusion: WM Binding increases with age and varies with GM 11C-PiB. These correlations should Be considered when using WM for normalization in 11C-PiB PET studies. The cereBellar crus1+crus2 showed no increase with age and cereBellar GM+WM showed minimal increase, supporting their use as reference regions for cross-sectional studies comparing wide age spans. In longitudinal studies, the increase in WM uptake may Be minimal in the short-term and thus using WM as a reference region in these studies seems reasonaBle. However, as participants age, the findings may Be affected By changes in WM uptake. Changes in WM 11C-PiB uptake may relate to disease progression, warranting examination of the causes of WM 11C-PiB uptake.
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clinicopathologic and 11c <B>PittsBurghB> <B>CompoundB> B implications of thal amyloid phase across the alzheimer s disease spectrum
Brain, 2015Co-Authors: Melissa E Murray, Val J Lowe, Neill R Graffradford, Amanda M Liesinger, Ashley Cannon, Scott A Przybelski, Bhupendra Rawal, Joseph E Parisi, Ronald C Petersen, Kejal KantarciAbstract:Thal amyloid phase, which descriBes the pattern of progressive amyloid-β plaque deposition in Alzheimer’s disease, was incorporated into the latest National Institute of Ageing – Alzheimer’s Association neuropathologic assessment guidelines. Amyloid Biomarkers (positron emission tomography and cereBrospinal fluid) were included in clinical diagnostic guidelines for Alzheimer’s disease dementia puBlished By the National Institute of Ageing – Alzheimer’s Association and the International Work group. Our first goal was to evaluate the correspondence of Thal amyloid phase to Braak tangle stage and ante-mortem clinical characteristics in a large autopsy cohort. Second, we examined the relevance of Thal amyloid phase in a prospectively-followed autopsied cohort who underwent ante-mortem 11C-<B>PittsBurghB> <B>CompoundB> B imaging; using the large autopsy cohort to Broaden our perspective of 11C-<B>PittsBurghB> <B>CompoundB> B results. The Mayo Clinic Jacksonville Brain Bank case series ( n = 3618) was selected regardless of ante-mortem clinical diagnosis and neuropathologic co-morBidities, and all assigned Thal amyloid phase and Braak tangle stage using thioflavin-S fluorescent microscopy. 11C-<B>PittsBurghB> <B>CompoundB> B studies from Mayo Clinic Rochester were availaBle for 35 participants scanned within 2 years of death. Cortical 11C-<B>PittsBurghB> <B>CompoundB> B values were calculated as a standard uptake value ratio normalized to cereBellum grey/white matter. In the high likelihood Alzheimer’s disease Brain Bank cohort ( n = 1375), cases with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE -e4 positive. Regression modelling in these Alzheimer’s disease cases, showed that Braak tangle stage, But not Thal amyloid phase predicted age at onset, disease duration, and final Mini-Mental State Examination score. In contrast, Thal amyloid phase, But not Braak tangle stage or cereBral amyloid angiopathy predicted 11C-<B>PittsBurghB> <B>CompoundB> B standard uptake value ratio. In the 35 cases with ante-mortem amyloid imaging, a transition Between Thal amyloid phases 1 to 2 seemed to correspond to 11C-<B>PittsBurghB> <B>CompoundB> B standard uptake value ratio of 1.4, which when using our pipeline is the cut-off point for detection of clear amyloid-positivity regardless of clinical diagnosis. Alzheimer’s disease cases who were older and were APOE -e4 negative tended to have lower amyloid phases. Although Thal amyloid phase predicted clinical characteristics of Alzheimer’s disease patients, the pre-mortem clinical status was driven By Braak tangle stage. Thal amyloid phase correlated Best with 11C-<B>PittsBurghB> <B>CompoundB> B values, But not Braak tangle stage or cereBral amyloid angiopathy. The 11C-<B>PittsBurghB> <B>CompoundB> B cut-off point value of 1.4 was approximately equivalent to a Thal amyloid phase of 1–2. * ABBreviations : CERAD : Consortium to EstaBlish a Registry for Alzheimer's Disease MMSE : Mini-Mental State Examination NIA-AA : National Institute on Ageing–Alzheimer’s Association NFT : neurofiBrillary tangle PiB : 11C-<B>PittsBurghB> <B>CompoundB> B SUV : standard uptake value
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Clinicopathologic and 11C-<B>PittsBurghB> <B>CompoundB> B implications of Thal amyloid phase across the Alzheimer’s disease spectrum
Brain, 2015Co-Authors: Melissa E Murray, Val J Lowe, Amanda M Liesinger, Ashley Cannon, Scott A Przybelski, Bhupendra Rawal, Joseph E Parisi, Ronald C Petersen, Neill R. Graff-radford, Kejal KantarciAbstract:Thal amyloid phase, which descriBes the pattern of progressive amyloid-β plaque deposition in Alzheimer’s disease, was incorporated into the latest National Institute of Ageing – Alzheimer’s Association neuropathologic assessment guidelines. Amyloid Biomarkers (positron emission tomography and cereBrospinal fluid) were included in clinical diagnostic guidelines for Alzheimer’s disease dementia puBlished By the National Institute of Ageing – Alzheimer’s Association and the International Work group. Our first goal was to evaluate the correspondence of Thal amyloid phase to Braak tangle stage and ante-mortem clinical characteristics in a large autopsy cohort. Second, we examined the relevance of Thal amyloid phase in a prospectively-followed autopsied cohort who underwent ante-mortem 11C-<B>PittsBurghB> <B>CompoundB> B imaging; using the large autopsy cohort to Broaden our perspective of 11C-<B>PittsBurghB> <B>CompoundB> B results. The Mayo Clinic Jacksonville Brain Bank case series ( n = 3618) was selected regardless of ante-mortem clinical diagnosis and neuropathologic co-morBidities, and all assigned Thal amyloid phase and Braak tangle stage using thioflavin-S fluorescent microscopy. 11C-<B>PittsBurghB> <B>CompoundB> B studies from Mayo Clinic Rochester were availaBle for 35 participants scanned within 2 years of death. Cortical 11C-<B>PittsBurghB> <B>CompoundB> B values were calculated as a standard uptake value ratio normalized to cereBellum grey/white matter. In the high likelihood Alzheimer’s disease Brain Bank cohort ( n = 1375), cases with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE -e4 positive. Regression modelling in these Alzheimer’s disease cases, showed that Braak tangle stage, But not Thal amyloid phase predicted age at onset, disease duration, and final Mini-Mental State Examination score. In contrast, Thal amyloid phase, But not Braak tangle stage or cereBral amyloid angiopathy predicted 11C-<B>PittsBurghB> <B>CompoundB> B standard uptake value ratio. In the 35 cases with ante-mortem amyloid imaging, a transition Between Thal amyloid phases 1 to 2 seemed to correspond to 11C-<B>PittsBurghB> <B>CompoundB> B standard uptake value ratio of 1.4, which when using our pipeline is the cut-off point for detection of clear amyloid-positivity regardless of clinical diagnosis. Alzheimer’s disease cases who were older and were APOE -e4 negative tended to have lower amyloid phases. Although Thal amyloid phase predicted clinical characteristics of Alzheimer’s disease patients, the pre-mortem clinical status was driven By Braak tangle stage. Thal amyloid phase correlated Best with 11C-<B>PittsBurghB> <B>CompoundB> B values, But not Braak tangle stage or cereBral amyloid angiopathy. The 11C-<B>PittsBurghB> <B>CompoundB> B cut-off point value of 1.4 was approximately equivalent to a Thal amyloid phase of 1–2. * ABBreviations : CERAD : Consortium to EstaBlish a Registry for Alzheimer's Disease MMSE : Mini-Mental State Examination NIA-AA : National Institute on Ageing–Alzheimer’s Association NFT : neurofiBrillary tangle PiB : 11C-<B>PittsBurghB> <B>CompoundB> B SUV : standard uptake value
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Clinicopathologic and 11C-<B>PittsBurghB> <B>CompoundB> B implications of Thal amyloid phase across the Alzheimer's disease spectrum.
Brain : a journal of neurology, 2015Co-Authors: Melissa E Murray, Val J Lowe, Amanda M Liesinger, Ashley Cannon, Scott A Przybelski, Bhupendra Rawal, Joseph E Parisi, Ronald C Petersen, Neill R. Graff-radford, Kejal KantarciAbstract:Thal amyloid phase, which descriBes the pattern of progressive amyloid-β plaque deposition in Alzheimer's disease, was incorporated into the latest National Institute of Ageing - Alzheimer's Association neuropathologic assessment guidelines. Amyloid Biomarkers (positron emission tomography and cereBrospinal fluid) were included in clinical diagnostic guidelines for Alzheimer's disease dementia puBlished By the National Institute of Ageing - Alzheimer's Association and the International Work group. Our first goal was to evaluate the correspondence of Thal amyloid phase to Braak tangle stage and ante-mortem clinical characteristics in a large autopsy cohort. Second, we examined the relevance of Thal amyloid phase in a prospectively-followed autopsied cohort who underwent ante-mortem (11)C-<B>PittsBurghB> <B>CompoundB> B imaging; using the large autopsy cohort to Broaden our perspective of (11)C-<B>PittsBurghB> <B>CompoundB> B results. The Mayo Clinic Jacksonville Brain Bank case series (n = 3618) was selected regardless of ante-mortem clinical diagnosis and neuropathologic co-morBidities, and all assigned Thal amyloid phase and Braak tangle stage using thioflavin-S fluorescent microscopy. (11)C-<B>PittsBurghB> <B>CompoundB> B studies from Mayo Clinic Rochester were availaBle for 35 participants scanned within 2 years of death. Cortical (11)C-<B>PittsBurghB> <B>CompoundB> B values were calculated as a standard uptake value ratio normalized to cereBellum grey/white matter. In the high likelihood Alzheimer's disease Brain Bank cohort (n = 1375), cases with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE-ε4 positive. Regression modelling in these Alzheimer's disease cases, showed that Braak tangle stage, But not Thal amyloid phase predicted age at onset, disease duration, and final Mini-Mental State Examination score. In contrast, Thal amyloid phase, But not Braak tangle stage or cereBral amyloid angiopathy predicted (11)C-<B>PittsBurghB> <B>CompoundB> B standard uptake value ratio. In the 35 cases with ante-mortem amyloid imaging, a transition Between Thal amyloid phases 1 to 2 seemed to correspond to (11)C-<B>PittsBurghB> <B>CompoundB> B standard uptake value ratio of 1.4, which when using our pipeline is the cut-off point for detection of clear amyloid-positivity regardless of clinical diagnosis. Alzheimer's disease cases who were older and were APOE-ε4 negative tended to have lower amyloid phases. Although Thal amyloid phase predicted clinical characteristics of Alzheimer's disease patients, the pre-mortem clinical status was driven By Braak tangle stage. Thal amyloid phase correlated Best with (11)C-<B>PittsBurghB> <B>CompoundB> B values, But not Braak tangle stage or cereBral amyloid angiopathy. The (11)C-<B>PittsBurghB> <B>CompoundB> B cut-off point value of 1.4 was approximately equivalent to a Thal amyloid phase of 1-2.