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Abstract Details

Plasma Biomarkers Predict Pre-clinical Amyloid- and Tau-PET in a Cognitively Healthy Cohort: The Framingham Heart Study
Aging, Dementia, Cognitive, and Behavioral Neurology
P1 - Poster Session 1 (8:00 AM-9:00 AM)
9-003

Dementia is a significant contributor to disability worldwide . In addition to neurodegeneration (Aβ and tau), other pathways (e.g. inflammation, vascular injury) likely play important roles in dementia pathogenesis. Identifying blood biomarkers for preclinical disease can inform our understanding of biological pathways underpinning dementia and identify opportunities for disease modification.

To identify plasma biomarkers predictive of amyloid- and tau-PET burden in cognitively healthy adults.

We measured 126 proteins in  279 dementia- and stroke-free Framingham Generation 3 cohort participants (136 women, mean age 45 [SD 8]) with available stored blood samples (2002-2005) and available 11C-Pittsburgh Compound-B (PiB)-PET and/or 18F-Flortaucipir (FTP)-PET scans completed a mean of 8.6 years after blood sampling. Linear mixed effect regression with family structure modelled as random effect between individual log transformed biomarkers and amyloid deposition (frontal, lateral temporal and retrosplenial cortices [FLR]; posterior cingulate (PC); and precuneus) and tau deposition (entorhinal cortex [ERC]; and global deposition was performed. Results were corrected for multiple testing (Bonferroni correction).

A total of 63 biomarkers demonstrated significant associations with amyloid- or tau-PET deposition. Plasma total tau (t-tau), serum receptor for advanced glycation products (sRAGE) and insulin predicted amyloid deposition in all measured regions (FLR (ß±SE, p): insulin [-0.15±0.06, p=0.008], sRAGE [-0.140±0.06, p=0.021], t-tau [0.10±0.05, .p= 0.036]).

9 biomarkers were associated with entorhinal and global tau, including growth differentiation factor-15 (ERC [ß±SE, p]: -0.014±0.07, p= 0.04), lysine deficient protein kinase-1 (WNK1) (ERC [ß±SE, p]: 0.52±0.25, p=0.03] and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (ERC [ß±SE, p]: 0.16±0.07, p=0.01).

Plasma t-tau, sRAGE (marker of hyperglycemia and inflammation) and insulin predicted pre-clinical amyloid-PET burden, while 9 biomarkers, including GDF-15, WNK-1 and nt-proBNP (markers of inflammation and vascular risk) predicted preclinical tau burden. These biomarkers offer potential in identifying preclinical stages of dementia but will require validation in other cohorts.

Authors/Disclosures
Martin D. Mulligan (University of Galway)
PRESENTER
Mr. Mulligan has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Claudia L. Satizabal, PhD (UT Health San Antonio) The institution of Dr. Satizabal has received research support from NIH and TARCC.
Keith A. Johnson, MD (MGH) Dr. Johnson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Johnson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. An immediate family member of Dr. Johnson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AC Immune. An immediate family member of Dr. Johnson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. An immediate family member of Dr. Johnson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prothena. An immediate family member of Dr. Johnson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NervGen. An immediate family member of Dr. Johnson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Oligomerix. Dr. Johnson has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AC Immune. The institution of Dr. Johnson has received research support from National Institute on Aging. The institution of an immediate family member of Dr. Johnson has received research support from Alzheimer's Association. The institution of an immediate family member of Dr. Johnson has received research support from Eli Lilly and Co. The institution of Dr. Johnson has received research support from Eisai. The institution of an immediate family member of Dr. Johnson has received research support from Eisai.
No disclosure on file
Sudha Seshadri, MD, FAAN (Glenn Biggs Institute for Alzheimer'S and Neurodegenerative Diseases) Dr. Seshadri has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Seshadri has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. The institution of Dr. Seshadri has received research support from NIH. The institution of Dr. Seshadri has received research support from Alzheimer Association.
Emer McGrath, MBChB (HRB Clinical Research Facility, University of Galway) Dr. McGrath has nothing to disclose.