title: Cerebral cortical Aβ42 and PHF-τ in 325 consecutive brain autopsies stratified by diagnosis, location, and APOE.
abstract: We used a novel approach to molecular quantification in standard fixed and embedded tissue to measure amyloid β 42 (Aβ(42)) and paired helical filament-τ (PHF-τ) in frontal, temporal, and parietal cortices from 325 consecutive brain autopsies collected as part of a population-based study of brain aging and incident dementia in the Seattle area. We observed significant effects of APOE ε4 on Aβ(42) levels in both diagnostic groups by disease stage and region. In contrast, we did not observe a significant effect of APOE ε4 on PHF-τ levels by disease stage in any region. Levels of Aβ(42) and PHF-τ in cerebral cortex were correlated more strongly in the Dementia group, and these measures had independent explanatory power for dementia beyond those of standard neuropathologic indices. Associations between Lewy body disease and Aβ(42) or PHF-τ levels and between Aβ(42) levels and microvascular brain injury suggested that these comorbid diseases enhanced the penetrance of Alzheimer disease. Our novel approach brings additional insights into the molecular pathogenesis of common causes of dementia and may serve as a platform for future studies pursuing associations between molecular changes in Alzheimer disease and genetic or environmental risk.
authors.affiliation: From the Departments of Pathology (NP, CDK, LFG-C, JH, SR, KH, KSM, TJM) and Medicine (PKC), University of Washington; and Group Health Research Institute (EBL), Seattle, Washington; and Department of Pathology, University of Utah, Salt Lake City, Utah (JAS).
authors.forename: Nadia
authors.initials: N
authors.lastname: Postupna
authors.forename: Christopher Dirk
authors.initials: CD
authors.lastname: Keene
authors.forename: Paul K
authors.initials: PK
authors.lastname: Crane
authors.forename: Luis F
authors.initials: LF
authors.lastname: Gonzalez-Cuyar
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Sonnen
authors.forename: Jessica
authors.initials: J
authors.lastname: Hewitt
authors.forename: Samantha
authors.initials: S
authors.lastname: Rice
authors.forename: Kimberly
authors.initials: K
authors.lastname: Howard
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Montine
authors.forename: Eric B
authors.initials: EB
authors.lastname: Larson
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics*; D001344:Autopsy; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D018672:Community Health Planning; D003704:Dementia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism*; D012720:Severity of Illness Index; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; C054369:MAPT protein, human; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D016875:tau Proteins