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dc.contributor.authorDesikan, Rahul S.
dc.contributor.authorSchmansky, Nicholas J.
dc.contributor.authorCabral, Howard J.
dc.contributor.authorHess, Christopher P.
dc.contributor.authorWeiner, Michael W.
dc.contributor.authorKemper, Thomas L.
dc.contributor.authorDale, Anders M.
dc.contributor.authorSabuncu, Mert R
dc.contributor.authorthe Alzheimer’s Disease Neuroimaging Initiative
dc.contributor.authorReuter, Martin
dc.contributor.authorBiffi, Alessandro
dc.contributor.authorAnderson, Christopher David
dc.contributor.authorRosand, Jonathan
dc.contributor.authorSalat, David H.
dc.contributor.authorSperling, Reisa Anne
dc.contributor.authorFischl, Bruce R.
dc.date.accessioned2011-07-14T17:22:16Z
dc.date.issued2010
dc.identifier.citationDesikan, Rahul S., Mert R. Sabuncu, Nicholas J. Schmansky, Martin Reuter, Howard J. Cabral, Christopher P. Hess, Michael W. Weiner, et al. 2010. Selective Disruption of the Cerebral Neocortex in Alzheimer's Disease. PLoS ONE 5(9): e12853.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:5026249
dc.description.abstractBackground: 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 Aβ 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.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0012853en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944799/pdf/en_US
dash.licenseLAA
dc.subjectneurological disordersen_US
dc.subjectneuroscienceen_US
dc.subjectneurology of disease and regenerationen_US
dc.subjectAlzheimer diseaseen_US
dc.subjectcognitive neurology and dementiaen_US
dc.titleSelective Disruption of the Cerebral Neocortex in Alzheimer's Diseaseen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorFischl, Bruce R.
dc.date.available2011-07-14T17:22:16Z
dash.affiliation.otherHMS^Radiology-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Health Sciences and Technologyen_US
dc.identifier.doi10.1371/journal.pone.0012853*
dash.authorsorderedfalse
dash.contributor.affiliatedSabuncu, Mert R
dash.contributor.affiliatedAnderson, Christopher
dash.contributor.affiliatedRosand, Jonathan
dash.contributor.affiliatedBiffi, Alessandro
dash.contributor.affiliatedReuter, Martin
dash.contributor.affiliatedSalat, David
dash.contributor.affiliatedFischl, Bruce
dash.contributor.affiliatedSperling, Reisa


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