OO010 - EXAMINING THE ASSOCIATION BETWEEN BLOOD-BASED BIOMARKERS AND HUMAN POST-MORTEM NEUROPATHOLOGY IN THE UNIVERSITY OF KENTUCKY ALZHEIMER’S DISEASE RESEARCH CENTER AUTOPSY COHORT (ID 270)

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Abstract

Aims

Identification of minimally invasive, readily obtained, biomarkers for Alzheimer’s disease and related dementias is a critical need for the eventual precision medicine approach to preventing and treating dementia. The goal of this study is to evaluate the association of angiogenic, inflammatory, and neurodegenerative plasma biomarkers with human post-mortem AD and vascular neuropathology.

Methods

Plasma samples within two-years of death were obtained from the University of Kentucky Alzheimer’s Disease Research Center (UK-ADRC) autopsy cohort. Evaluation of Thal, Braak, CERAD, arteriolosclerosis, amyloid angiopathy, and chronic vascular grade was performed by UK-ADRC neuropathologists. Plasma biomarkers were assessed with Quanterix SiMoA assays and log transformed. The association of plasma markers with neuropathology was assessed via proportional odds and binary logistic regressions adjusted for age.

Results

Included cases (N = 90) showed t-Tau/Ab42 ratio and GFAP were positively associated with more severe AD neuropathologic change, while Ab42/Ab40 ratio was inversely associated. PlGF, VEGF-A, and IL-6 were inversely associated with chronic vascular grade, while Ab42/Ab40 ratio demonstrated a positive association.

Conclusions

Our results confirm published antemortem plasma biomarker associations in an autopsy-confirmed cohort. Interestingly, we show that angiogenic (VEGF-A) and inflammatory (IL-6) biomarkers are inversely associated with vascular neuropathology. These data provide novel insights into plasma biomarker relationships with pathological hallmarks of dementia and will be explored further in a larger cohort.

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