Abstract Details

Title Alzheimer's Disease Pathology Burden Associated with Clinical Dementia Decreases with Age

Topic Aging and Dementia

Presentation(s) P04 - (-)

Poster/Presentation
Number 213

Objective

Background BACKGROUND: Age is the number one risk factor for Alzheimer's disease (AD). Previous studies suggest that AD pathological burden is a less salient etiological factor for dementia in older individuals. Few have objectively examined tissue markers of AD pathology in relation to dementia onset (DO) age.

Design/Methods DESIGN/METHODS: 285 Oregon AD Center volunteers underwent brain autopsy with both standard neuropathological examination and immunochemical analysis of the detergent-insoluble fraction of frontal cortex. 142 had significant AD pathology (?Braak IV). 110 had dementia, 32 did not. 3 dementia groups were created based on DO: Young (DO < 60, n = 22), Young Old (YO, DO 60-74, n = 46), and Old Old (OO, DO 75+, n = 42). Detergent-insoluble quantitative tau (qTau) and A[szlig]42 (qA[szlig]42) were determined by ELISA. Vascular disease was determined by standard histopathologic examination. T-tests and ANOVA's determined group differences in AD proteins.

Results RESULTS: Adjusting for gender, dementia duration, brain weight, and APO?4, qTau decreased with increasing DO. Similarly, qA[szlig]42 was increased in the Young group compared with YO or OO groups. qA[szlig]42 and qTau were elevated in all dementia groups compared with nondemented elderly. In a final model comparing differences between YO and OO groups, older DO was associated with decreased dementia duration, vascular pathology, and no APO?4 allele. In this model older DO was associated with decreased qTau but not Braak score or either qA[szlig]42 or CERAD score.

Conclusions CONCLUSIONS: AD pathology in dementia decreases with age, a finding not fully accounted for by brain atrophy and vascular disease. Results suggest that tau is a more sensitive marker of dementia in the aging brain, and that immunochemical markers may be more clinically relevant than traditional scoring measures. Further studies investigating tissue markers accounting for dementia risk are needed.

Authors/Disclosures
Lisa Silbert, MD, FAAN (OHSU) PRESENTER	The institution of Dr. Silbert has received research support from the NIH. Dr. Silbert has received personal compensation in the range of $0-$499 for serving as a Peer Reviewer, study section with NIH.
Tomas Uher	Tomas Uher has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Tomas Uher has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol myers. Tomas Uher has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Tomas Uher has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. The institution of Tomas Uher has received research support from Novartis.
Jeffrey A. Kaye, MD, FAAN (Oregon Hlth Sci Univ.)	Dr. Kaye has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Kaye has stock in Life Analytics. The institution of Dr. Kaye has received research support from NIH. The institution of Dr. Kaye has received research support from NSF. The institution of Dr. Kaye has received research support from AbbVie. Dr. Kaye has received intellectual property interests from a discovery or technology relating to health care.
Deniz Erten-Lyons, MD, FAAN (FDA)	Dr. Erten-Lyons has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Acadia Pharamceuticals.
Hiroko H. Dodge, PhD (Massachusetts General Hospital)	No disclosure on file
Joseph F. Quinn, MD, FAAN (OHSU Neurology)	Dr. Quinn has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Retrophin. Dr. Quinn has received personal compensation in the range of $500-$4,999 for serving as a DSMB with Alzheimer's Disease Cooperative Study. Dr. Quinn has received personal compensation in the range of $500-$4,999 for serving as a DSMB with Alzheimer's Therapeutic Research Institute. Dr. Quinn has a non-compensated relationship as a consultant with Cognition Therapeutics that is relevant to AAN interests or activities.
Barry S. Oken, MD, PhD, FAAN (Oregon Health & Science Univ.)	Dr. Oken has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Randall L. Woltjer (Oregon Health & Science University)	Randall L. Woltjer has nothing to disclose.

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