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Maria Thom - One of the best experts on this subject based on the ideXlab platform.

  • Hyperphosphorylated tau in patients with refractory epilepsy correlates with cognitive decline: a study of temporal lobe resections
    Brain, 2016
    Co-Authors: Xin You Tai, Joan Liu, Pamela J Thompson, Matthias J Koepp, John S. Duncan, Nick C. Fox, Sallie Baxendale, Cheryl Reeves, Zuzanna Michalak, Maria Thom
    Abstract:

    SEE BERNASCONI DOI101093/AWW202 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Temporal lobe epilepsy, the most prevalent form of chronic focal epilepsy, is associated with a high prevalence of cognitive impairment but the responsible underlying pathological mechanisms are unknown. Tau, the microtubule-associated protein, is a hallmark of several neurodegenerative diseases including Alzheimer's disease and chronic traumatic encephalopathy. We hypothesized that hyperphosphorylated tau pathology is associated with cognitive decline in temporal lobe epilepsy and explored this through clinico-pathological study. We first performed pathological examination on tissue from 33 patients who had undergone temporal lobe resection between ages 50 and 65 years to treat drug-refractory temporal lobe epilepsy. We identified hyperphosphorylated tau protein using AT8 immunohistochemistry and compared this distribution to Braak patterns of Alzheimer's disease and patterns of chronic traumatic encephalopathy. We quantified tau pathology using a modified tau score created specifically for analysis of temporal lobectomy tissue and the Braak Staging, which was limited without extra-temporal brain areas available. Next, we correlated tau pathology with pre- and postoperative cognitive test scores and clinical risk factors including age at time of surgery, duration of epilepsy, history of secondary generalized seizures, history of head injury, handedness and side of surgery. Thirty-one of 33 cases (94%) showed hyperphosphorylated tau pathology in the form of neuropil threads and neurofibrillary tangles and pre-tangles. Braak stage analysis showed 12% of our epilepsy cohort had a Braak Staging III-IV compared to an age-matched non-epilepsy control group from the literature (8%). We identified a mixture of tau pathology patterns characteristic of Alzheimer's disease and chronic traumatic encephalopathy. We also found unusual patterns of subpial tau deposition, sparing of the hippocampus and co-localization with mossy fibre sprouting, a feature of temporal lobe epilepsy. We demonstrated that the more extensive the tau pathology, the greater the decline in verbal learning (Spearman correlation, r = -0.63), recall (r = -0.44) and graded naming test scores (r = -0.50) over 1-year post-temporal lobe resection (P < 0.05). This relationship with tau burden was also present when examining decline in verbal learning from 3 months to 1 year post-resection (r = -0.54). We found an association between modified tau score and history of secondary generalized seizures (likelihood-ratio χ(2), P < 0.05) however there was no clear relationship between tau pathology and other clinical risk factors assessed. Our findings suggest an epilepsy-related tauopathy in temporal lobe epilepsy, which contributes to accelerated cognitive decline and has diagnostic and treatment implications.

  • neurofibrillary tangle pathology and Braak Staging in chronic epilepsy in relation to traumatic brain injury and hippocampal sclerosis a post mortem study
    Brain, 2011
    Co-Authors: Maria Thom, Joan Liu, Pamela J Thompson, R Phadke, Marta Narkiewicz, L Martinian, Derek Marsdon, Matthias J Koepp, Luis O Caboclo, Claudia B Catarino
    Abstract:

    The long-term pathological effects of chronic epilepsy on normal brain ageing are unknown. Previous clinical and epidemiological studies show progressive cognitive decline in subsets of patients and an increased prevalence of Alzheimer's disease in epilepsy. In a post-mortem series of 138 patients with long-term, mainly drug-resistant epilepsy, we carried out Braak Staging for Alzheimer's disease neurofibrillary pathology using tau protein immunohistochemistry. The stages were compared with clinicopathological factors, including seizure history and presence of old traumatic brain injury. Overall, 31% of cases were Braak Stage 0, 36% Stage I/II, 31% Stage III/IV and 2% Stage V/VI. The mean age at death was 56.5 years and correlated with Braak stage (P < 0.001). Analysis of Braak stages within age groups showed a significant increase in mid-Braak stages (III/IV), in middle age (40-65 years) compared with data from an ageing non-epilepsy series (P < 0.01). There was no clear relationship between seizure type (generalized or complex partial), seizure frequency, age of onset and duration of epilepsy with Braak stage although higher Braak stages were noted with focal more than with generalized epilepsy syndromes (P < 0.01). In 30% of patients, there was pathological evidence of traumatic brain injury that was significantly associated with higher Braak stages (P < 0.001). Cerebrovascular disease present in 40.3% and cortical malformations in 11.3% were not significantly associated with Braak stage. Astrocytic-tau protein correlated with the presence of both traumatic brain injury (P < 0.01) and high Braak stage (P < 0.001). Hippocampal sclerosis, identified in 40% (bilateral in 48%), was not associated with higher Braak stages, but asymmetrical patterns of tau protein accumulation within the sclerotic hippocampus were noted. In over half of patients with cognitive decline, the Braak stage was low indicating causes other than Alzheimer's disease pathology. In summary, there is evidence of accelerated brain ageing in severe chronic epilepsy although progression to high Braak stages was infrequent. Traumatic brain injury, but not seizures, was associated with tau protein accumulation in this series. It is likely that Alzheimer's disease pathology is not the sole explanation for cognitive decline associated with epilepsy.

Suzanne L Baker - One of the best experts on this subject based on the ideXlab platform.

  • Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease
    NeuroImage, 2017
    Co-Authors: Anne Maass, Samuel N Lockhart, Suzanne L Baker, Susan M. Landau, Andy Horng, Renaud La Joie, Gil D. Rabinovici, William J. Jagust
    Abstract:

    The recent development of tau-specific positron emission tomography (PET) tracers enables in vivo quantification of regional tau pathology, one of the key lesions in Alzheimer's disease (AD). Tau PET imaging may become a useful biomarker for clinical diagnosis and tracking of disease progression but there is no consensus yet on how tau PET signal is best quantified. The goal of the current study was to evaluate multiple whole-brain and region-specific approaches to detect clinically relevant tau PET signal. Two independent cohorts of cognitively normal adults and amyloid-positive (Aβ+) patients with mild cognitive impairment (MCI) or AD-dementia underwent [18F]AV-1451 PET. Methods for tau tracer quantification included: (i) in vivo Braak Staging, (ii) regional uptake in Braak composite regions, (iii) several whole-brain measures of tracer uptake, (iv) regional uptake in AD-vulnerable voxels, and (v) uptake in a priori defined regions. Receiver operating curves characterized accuracy in distinguishing Aβ- controls from AD/MCI patients and yielded tau positivity cutoffs. Clinical relevance of tau PET measures was assessed by regressions against cognition and MR imaging measures. Key tracer uptake patterns were identified by a factor analysis and voxel-wise contrasts. Braak Staging, global and region-specific tau measures yielded similar diagnostic accuracies, which differed between cohorts. While all tau measures were related to amyloid and global cognition, memory and hippocampal/entorhinal volume/thickness were associated with regional tracer retention in the medial temporal lobe. Key regions of tau accumulation included medial temporal and inferior/middle temporal regions, retrosplenial cortex, and banks of the superior temporal sulcus. Our data indicate that whole-brain tau PET measures might be adequate biomarkers to detect AD-related tau pathology. However, regional measures covering AD-vulnerable regions may increase sensitivity to early tau PET signal, atrophy and memory decline.

  • PET Imaging of Tau Deposition in the Aging Human Brain
    Neuron, 2016
    Co-Authors: Michael Scholl, Samuel N Lockhart, Daniel R Schonhaut, Mustafa Janabi, Rik Ossenkoppele, Suzanne L Baker, James P. O'neil, Jacob W. Vogel, Jamie Faria, Henry Schwimmer
    Abstract:

    Tau pathology is a hallmark of Alzheimer's disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent (18)F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak Staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition.

  • pet imaging of tau deposition in the aging human brain
    Neuron, 2016
    Co-Authors: Michael Scholl, Samuel N Lockhart, Daniel R Schonhaut, James P Oneil, Mustafa Janabi, Rik Ossenkoppele, Suzanne L Baker
    Abstract:

    Tau pathology is a hallmark of Alzheimer's disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent (18)F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak Staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition.

Rik Ossenkoppele - One of the best experts on this subject based on the ideXlab platform.

  • Patient-centered connectivity-based prediction of tau pathology spread in Alzheimer's disease
    Science advances, 2020
    Co-Authors: Nicolai Franzmeier, Rik Ossenkoppele, Anna Rubinski, Martin Dichgans, Anna Dewenter, Lukas Frontzkowski, Julia Neitzel, Ruben Smith, Olof Strandberg, Katharina Buerger
    Abstract:

    In Alzheimer's disease (AD), the Braak Staging scheme suggests a stereotypical tau spreading pattern that does, however, not capture interindividual variability in tau deposition. This complicates the prediction of tau spreading, which may become critical for defining individualized tau-PET readouts in clinical trials. Since tau is assumed to spread throughout connected regions, we used functional connectivity to improve tau spreading predictions over Braak Staging methods. We included two samples with longitudinal tau-PET from controls and AD patients. Cross-sectionally, we found connectivity of tau epicenters (i.e., regions with earliest tau) to predict estimated tau spreading sequences. Longitudinally, we found tau accumulation rates to correlate with connectivity strength to patient-specific tau epicenters. A connectivity-based, patient-centered tau spreading model improved the assessment of tau accumulation rates compared to Braak stage-specific readouts and reduced sample sizes by ~40% in simulated tau-targeting interventions. Thus, connectivity-based tau spreading models may show utility in clinical trials.

  • PET Imaging of Tau Deposition in the Aging Human Brain
    Neuron, 2016
    Co-Authors: Michael Scholl, Samuel N Lockhart, Daniel R Schonhaut, Mustafa Janabi, Rik Ossenkoppele, Suzanne L Baker, James P. O'neil, Jacob W. Vogel, Jamie Faria, Henry Schwimmer
    Abstract:

    Tau pathology is a hallmark of Alzheimer's disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent (18)F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak Staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition.

  • pet imaging of tau deposition in the aging human brain
    Neuron, 2016
    Co-Authors: Michael Scholl, Samuel N Lockhart, Daniel R Schonhaut, James P Oneil, Mustafa Janabi, Rik Ossenkoppele, Suzanne L Baker
    Abstract:

    Tau pathology is a hallmark of Alzheimer's disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent (18)F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak Staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition.

Michael Scholl - One of the best experts on this subject based on the ideXlab platform.

  • PET Imaging of Tau Deposition in the Aging Human Brain
    Neuron, 2016
    Co-Authors: Michael Scholl, Samuel N Lockhart, Daniel R Schonhaut, Mustafa Janabi, Rik Ossenkoppele, Suzanne L Baker, James P. O'neil, Jacob W. Vogel, Jamie Faria, Henry Schwimmer
    Abstract:

    Tau pathology is a hallmark of Alzheimer's disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent (18)F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak Staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition.

  • pet imaging of tau deposition in the aging human brain
    Neuron, 2016
    Co-Authors: Michael Scholl, Samuel N Lockhart, Daniel R Schonhaut, James P Oneil, Mustafa Janabi, Rik Ossenkoppele, Suzanne L Baker
    Abstract:

    Tau pathology is a hallmark of Alzheimer's disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent (18)F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak Staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition.

Paul G. Ince - One of the best experts on this subject based on the ideXlab platform.

  • Epidemiological pathology of Tau in the ageing brain: application of Staging for neuropil threads (BrainNet Europe protocol) to the MRC cognitive function and ageing brain study.
    Acta neuropathologica communications, 2016
    Co-Authors: Stephen B. Wharton, Thais Minett, David Drew, Gillian Forster, Fiona E. Matthews, Carol Brayne, Paul G. Ince
    Abstract:

    Deposition of abnormally phosphorylated tau (phospho-tau) occurs in Alzheimer’sdisease but also with brain ageing. The Braak Staging scheme focused on neurofibrillary tangles, butabundant p-tau is also present in neuropil threads, and a recent scheme has been proposed by theBrainNet Europe consortium for Staging tau pathology based on neuropil threads. We determined therelationship of threads to tangles, and the value of Staging for threads in an unselected population-representative ageing brain cohort. We also determined the prevalence of astroglial tau pathologies, and their relationship to neuronal tau. Phospho-tau pathology was determined by immunohistochemistry (AT8 antibody) in the MRC-CFAS neuropathology cohort. Neuropil threads were staged using the BrainNet Europe protocol for tau pathology, and compared with Braak tangle stages. Astroglial tau pathology was assessed in neo-cortical, mesial temporal and subcortical areas. Cases conformed well to the hierarchical neuropil threads Staging of the BrainNet Europe protocol and correlated strongly with Braak Staging (r=0.84, p