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Spreading of amyloid, tau, and microvascular pathology in alzheimer's disease: Findings from neuropathological and neuroimaging studies

Lookup NU author(s): Professor Johannes Attems


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© 2014 - IOS Press and the authors. All rights reserved. Primary pathologies including amyloid-β (Aβ) plaques and neurofibrillary tangles (NFT) develop many years before the onset of dementia symptoms in Alzheimer's disease (AD). Age-related small vessel disease (SVD) is common in elderly subjects and may contribute to the clinical syndrome of AD. Each type of pathology shows a specific spatiooral sequence of spreading in the brain. Here, we review neuropathological and neuroimaging findings (PET tracers of Aβ and NFT, MRI markers of SVD) to assess whether staging of these primary pathologies is useful to predict clinical symptoms in AD. On the basis of neuropathological data, early stages of Aβ plaque and NFT pathology distribution occur in preclinical AD, but advanced stages with spreading into further brain regions are associated with dementia symptoms. Amyloid PET presumably detects Aβ in advanced neuropathological Aβ stages, and increased global amyloid PET uptake is associated with clinical worsening in non-demented subjects. Tau PET may provide additional predictive value by detecting NFT in the allocortex. There is weak evidence that SVD is related to amyloid or NFT pathology. Global volume of MRI-assessed white matter hyperintensities (WMH) contribute in addition to biomarker levels of Aβ to predict cognitive decline. Regional differences of the effect of WMH on cognition have been demonstrated but are not yet established as a biomarker in AD. In conclusion, biomarkers for amyloid and tau pathology allow a distinction between early and advanced stages of AD, but a subgroup of pathologically identified preclinical AD cases is not identified by the currently available biomarkers.

Publication metadata

Author(s): Thal DR, Attems J, Ewers M

Publication type: Review

Publication status: Published

Journal: Journal of Alzheimer's Disease

Year: 2014

Volume: 42

Issue: s4

Pages: S421-S429

Acceptance date: 15/08/2014

ISSN (print): 1387-2877

ISSN (electronic): 1875-8908

Publisher: IOS Press


DOI: 10.3233/JAD-141461

PubMed id: 25227313