The Experts below are selected from a list of 365406 Experts worldwide ranked by ideXlab platform
Ralph A Nixon - One of the best experts on this subject based on the ideXlab platform.
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elevated levels of the endosomal lysosomal proteinase cathepsin d in cerebrospinal fluid in Alzheimer disease
Journal of Neurochemistry, 2002Co-Authors: A L Schwagerl, P S Mohan, Anne M Cataldo, Jeanpaul Vonsattel, Neil W Kowall, Ralph A NixonAbstract:: Lysosomal hydrolases are normally intracellular enzymes but are abundant extracellularly within senile plaques in Alzheimer disease and in other conditions where beta-amyloid accumulates. To examine whether acid hydrolases released from abnormal hydrolase-laden neurons are detectable in CSF, we measured levels of the major aspartic proteinase of lysosomes, cathepsin D (Cat D), in ventricular CSF collected after death from 30 patients with Alzheimer disease, 14 patients with Huntington disease, and seven patients with other neurodegenerative diseases. The levels of Cat D-immunoreactive protein, expressed as micrograms per milliliter of protein, determined by western blot immunoassay using a polyclonal antiserum against human brain Cat D, were more than fourfold higher in the Alzheimer patients than in the other patient groups (p < 0.0005). Cat D activity, assayed separately against [14C]methemoglobin at pH 3.2, was also significantly elevated but less than Cat D content. The lower specific activity of Cat D in Alzheimer CSF therefore indicated that the abnormally accumulated Cat D included a high proportion of inactive enzyme. These results indicate that abnormal Cat D release from affected neurons into the extracellular space is an active, ongoing process in Alzheimer brain. In addition, the levels of this enzyme and possibly other lysosomal hydrolases in CSF may prove to be useful biological markers of Alzheimer disease.
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widespread activation of calcium activated neutral proteinase calpain in the brain in Alzheimer disease a potential molecular basis for neuronal degeneration
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Kenichi Saito, John S Elce, James E Hamos, Ralph A NixonAbstract:Calcium-activated neutral proteinases (CANPs or calpains) are believed to be key enzymes in intracellular signaling cascades and potential mediators of calcium-induced neuronal degeneration. To investigate their involvement in Alzheimer disease, we identified three isoforms of muCANP (calpain I) in human postmortem brain corresponding to an 80-kDa precursor and two autolytically activated isoforms (78 and 76 kDa). As an index of changes in the in vivo activity of muCANP in Alzheimer disease, the ratio of the 76-kDa activated isoform of muCANP to its 80-kDa precursor was measured by immunoassay in selected brain regions from 22 individuals with Alzheimer disease and 18 normal controls. This muCANP activation ratio was elevated 3-fold in the prefrontal cortex from patients with Alzheimer disease but not from patients with Huntington disease. The activation ratio was also significantly elevated, but to a lesser degree, in brain regions where Alzheimer pathology is milder and has not led to overt neuronal degeneration. These findings indicate that muCANP activation is not simply a consequence of cellular degeneration but may be associated with dysfunction in many neurons before gross structural changes occur. The known influences of CANPs on cytoskeleton and membrane dynamics imply that persistent CANP activation may contribute to neurofibrillary pathology and abnormal amyloid precursor protein processing prior to causing synapse loss or cell death in the most vulnerable neuronal populations. Pharmacological modulation of the CANP system may merit consideration as a potential therapeutic strategy in Alzheimer disease.
Emanuel Weitschek - One of the best experts on this subject based on the ideXlab platform.
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a novel method and software for automatically classifying Alzheimers disease patients by magnetic resonance imaging analysis
Computer Methods and Programs in Biomedicine, 2017Co-Authors: F Previtali, Paola Bertolazzi, Giovanni Felici, Emanuel WeitschekAbstract:Supervised classification of Alzheimer disease patients.A novel technique for feature extraction from magnetic resonance images.Combination of key points spatial position and their distribution around the patients brain.Experimental evidence on real biomedical data sets.The method outperforms state-of-the-art approaches in terms of classification performance. Background and objectiveThe cause of the Alzheimers disease is poorly understood and to date no treatment to stop or reverse its progression has been discovered. In developed countries, the Alzheimers disease is one of the most financially costly diseases due to the requirement of continuous treatments as well as the need of assistance or supervision with the most cognitively demanding activities as time goes by. The objective of this work is to present an automated approach for classifying the Alzheimers disease from magnetic resonance imaging (MRI) patient brain scans. The method is fast and reliable for a suitable and straightforward deploy in clinical applications for helping diagnosing and improving the efficacy of medical treatments by recognising the disease state of the patient. MethodsMany features can be extracted from magnetic resonance images, but most are not suitable for the classification task. Therefore, we propose a new feature extraction technique from patients MRI brain scans that is based on a recent computer vision method, called Oriented FAST and Rotated BRIEF. The extracted features are processed with the definition and the combination of two new metrics, i.e., their spatial position and their distribution around the patients brain, and given as input to a function-based classifier (i.e., Support Vector Machines). ResultsWe report the comparison with recent state-of-the-art approaches on two established medical data sets (ADNI and OASIS). In the case of binary classification (case vs control), our proposed approach outperforms most state-of-the-art techniques, while having comparable results with the others. Specifically, we obtain 100% (97%) of accuracy, 100% (97%) sensitivity and 99% (93%) specificity for the ADNI (OASIS) data set. When dealing with three or four classes (i.e., classification of all subjects) our method is the only one that reaches remarkable performance in terms of classification accuracy, sensitivity and specificity, outperforming the state-of-the-art approaches. In particular, in the ADNI data set we obtain a classification accuracy, sensitivity and specificity of 99% while in the OASIS data set a classification accuracy and sensitivity of 77% and specificity of 79% when dealing with four classes. ConclusionsBy providing a quantitative comparison on the two established data sets with many state-of-the-art techniques, we demonstrated the effectiveness of our proposed approach in classifying the Alzheimers disease from MRI patient brain scans.
Irina Alafuzoff - One of the best experts on this subject based on the ideXlab platform.
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correlations between mini mental state examination score cerebrospinal fluid biomarkers and pathology observed in brain biopsies of patients with normal pressure hydrocephalus
Journal of Neuropathology and Experimental Neurology, 2015Co-Authors: Adila Elobeid, Katarina Laurell, Kristina Giuliana Cesarini, Irina AlafuzoffAbstract:Alzheimer disease (AD)-related pathology was assessed in cortical biopsy samples of 111 patients with idiopathic normal-pressure hydrocephalus. Alzheimer disease hallmark lesions-beta-amyloid (A be ...
Stanley I Rapoport - One of the best experts on this subject based on the ideXlab platform.
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corpus callosum atrophy is a possible indicator of region and cell type specific neuronal degeneration in Alzheimer disease a magnetic resonance imaging analysis
JAMA Neurology, 1998Co-Authors: Harald Hampel, Stefan J Teipel, Gene E Alexander, Barry Horwitz, Diane Teichberg, Mark B Schapiro, Stanley I RapoportAbstract:Background Pathological studies in Alzheimer disease indicate the specific loss of layer III and V large pyramidal neurons in association cortex. These neurons give rise to long corticocortical connections within and between the cerebral hemispheres. Objective To evaluate the corpus callosum as an in vivo marker for cortical neuronal loss. Method Using a new imaging technique, we measured region-specific corpus callosum atrophy in patients with Alzheimer disease and correlated the changes with neuropsychological functioning. Total cross-sectional area of the corpus callosum and areas of 5 callosal subregions were measured on midsagittal magnetic resonance imaging scans of 14 patients with Alzheimer disease (mean age, 64.4 years; Mini-Mental State Examination score, 11.4) and 22 healthy age- and sex-matched control subjects (mean age, 66.6 years; Mini-Mental State Examination score, 29.8). All subjects had minimal white matter changes. Results The total callosal area was significantly reduced in the patients with Alzheimer disease, with the greatest changes in the rostrum and splenium and relative sparing of the callosal body. Regional callosal atrophy correlated significantly with cognitive impairment in the patients with Alzheimer disease, but not with age or the white matter hyperintensities score. Conclusions Callosal atrophy in patients with Alzheimer disease with only minimal white matter changes may indicate loss of callosal efferent neurons in corresponding regions of the cortex. Because these neurons are a subset of corticocortical projecting neurons, region-specific callosal atrophy may serve as a marker of progressive neocortical disconnection in Alzheimer disease.
Stefan J Teipel - One of the best experts on this subject based on the ideXlab platform.
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corpus callosum atrophy is a possible indicator of region and cell type specific neuronal degeneration in Alzheimer disease a magnetic resonance imaging analysis
JAMA Neurology, 1998Co-Authors: Harald Hampel, Stefan J Teipel, Gene E Alexander, Barry Horwitz, Diane Teichberg, Mark B Schapiro, Stanley I RapoportAbstract:Background Pathological studies in Alzheimer disease indicate the specific loss of layer III and V large pyramidal neurons in association cortex. These neurons give rise to long corticocortical connections within and between the cerebral hemispheres. Objective To evaluate the corpus callosum as an in vivo marker for cortical neuronal loss. Method Using a new imaging technique, we measured region-specific corpus callosum atrophy in patients with Alzheimer disease and correlated the changes with neuropsychological functioning. Total cross-sectional area of the corpus callosum and areas of 5 callosal subregions were measured on midsagittal magnetic resonance imaging scans of 14 patients with Alzheimer disease (mean age, 64.4 years; Mini-Mental State Examination score, 11.4) and 22 healthy age- and sex-matched control subjects (mean age, 66.6 years; Mini-Mental State Examination score, 29.8). All subjects had minimal white matter changes. Results The total callosal area was significantly reduced in the patients with Alzheimer disease, with the greatest changes in the rostrum and splenium and relative sparing of the callosal body. Regional callosal atrophy correlated significantly with cognitive impairment in the patients with Alzheimer disease, but not with age or the white matter hyperintensities score. Conclusions Callosal atrophy in patients with Alzheimer disease with only minimal white matter changes may indicate loss of callosal efferent neurons in corresponding regions of the cortex. Because these neurons are a subset of corticocortical projecting neurons, region-specific callosal atrophy may serve as a marker of progressive neocortical disconnection in Alzheimer disease.
