Selective Disruption of the Cerebral Neocortex in Alzheimer's Disease


Show simple item record Desikan, Rahul S. en_US Sabuncu, Mert R. en_US Schmansky, Nicholas J. en_US Reuter, Martin en_US Cabral, Howard J. en_US Hess, Christopher P. en_US Weiner, Michael W. en_US Biffi, Alessandro en_US Anderson, Christopher D. en_US Rosand, Jonathan en_US Salat, David H. en_US Kemper, Thomas L. en_US Dale, Anders M. en_US Sperling, Reisa A. en_US Fischl, Bruce en_US 2012-01-11T16:18:19Z 2012-01-11T16:18:19Z 2010-9-23 en_US
dc.identifier.citation Desikan, Rahul S., Mert R. Sabuncu, Nicholas J. Schmansky, Martin Reuter, Howard J. Cabral, Christopher P. Hess, Michael W. Weiner, Alessandro Biffi, Christopher D. Anderson, Jonathan Rosand, David H. Salat, Thomas L. Kemper, Anders M. Dale, Reisa A. Sperling, Bruce Fischl. "Selective Disruption of the Cerebral Neocortex in Alzheimer's Disease" PLoS ONE 5(9): e12853. (2010) en_US
dc.identifier.issn 1932-6203 en_US
dc.description.abstract BACKGROUND. Alzheimer's disease (AD) and its transitional state mild cognitive impairment (MCI) are characterized by amyloid plaque and tau neurofibrillary tangle (NFT) deposition within the cerebral neocortex and neuronal loss within the hippocampal formation. However, the precise relationship between pathologic changes in neocortical regions and hippocampal atrophy is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS. In this study, combining structural MRI scans and automated image analysis tools with reduced cerebrospinal fluid (CSF) Aß levels, a surrogate for intra-cranial amyloid plaques and elevated CSF phosphorylated tau (p-tau) levels, a surrogate for neocortical NFTs, we examined the relationship between the presence of Alzheimer's pathology, gray matter thickness of select neocortical regions, and hippocampal volume in cognitively normal older participants and individuals with MCI and AD (n=724). Amongst all 3 groups, only select heteromodal cortical regions significantly correlated with hippocampal volume. Amongst MCI and AD individuals, gray matter thickness of the entorhinal cortex and inferior temporal gyrus significantly predicted longitudinal hippocampal volume loss in both amyloid positive and p-tau positive individuals. Amongst cognitively normal older adults, thinning only within the medial portion of the orbital frontal cortex significantly differentiated amyloid positive from amyloid negative individuals whereas thinning only within the entorhinal cortex significantly discriminated p-tau positive from p-tau negative individuals. CONCLUSIONS/SIGNIFICANCE. Cortical Aß and tau pathology affects gray matter thinning within select neocortical regions and potentially contributes to downstream hippocampal degeneration. Neocortical Alzheimer's pathology is evident even amongst older asymptomatic individuals suggesting the existence of a preclinical phase of dementia. en_US
dc.description.sponsorship National Center for Research Resources (P41-RR14075, R01 RR 16594-01A1, NCRR BIRN Morphometric Project BIRN002, U24 RR021382); National Institute for Biomedical Imaging and Bioengineering (R01 EB001550, R01EB006758); National Institute for Neurological Disorders and Stroke (R01 NS052585-01); Mental Illness and Neuroscience Discovery Institute; National Institute on Aging (P50 AG05681, P01 AG03991, AG02238, AG021910); The Autism & Dyslexia Project; Alzheimer's Disease Neuroimaging Initiative; National Institutes of Health (U01 AG024904); AstraZeneca AB; Bayer Schering Pharma AG; Bristol-Myers Squibb; Eisai Global Clinical Development; Elan Corporation; Genentech; GE Healthcare; GlaxoSmithKline; Innogenetics; Johnson and Johnson; Eli Lilly and Co.; Medpace, Inc.; Merck and Co. Inc.; Novartis AG; Pfizer Inc; F. Hoffman-La Roche; Schering-Plough; Synarc, Inc.; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; U.S. Food and Drug Administration. en_US
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.rights Desikan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en_US
dc.title Selective Disruption of the Cerebral Neocortex in Alzheimer's Disease en_US
dc.type article en_US
dc.identifier.doi 10.1371/journal.pone.0012853 en_US
dc.identifier.pubmedid 20886094 en_US
dc.identifier.pmcid 2944799 en_US

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