Hippocampal tau pathology burden in Lewy body disorders

Objective: To compare regional patterns of tau and alpha-synuclein (SYN) pathology in hippocampal subfields (HIPPsf) in Lewy body disorders (LBD: Parkinson’s disease dementia-PDD, Dementia with Lewy bodies-DLB). Background: Alzheimer’s disease (AD) tau co-pathology is common in LBD and predicts poor prognosis. We previously found the neocortical distribution of tau mapped closely with SYN and diverged from the distribution of tau in AD. Here we use digital pathology in hippocampal-subfields (HIPPsf) to test whether prominent SYN pathology in CA2/3 associates with Tau in LBD, and if HIPPsf tau in LBD differs from AD. Design/Methods: Forty-nine autopsy-confirmed LBD subjects were categorized using neuropathological criteria as either medium/high (LBD+AD=22: Braak(B) stages B2–3) or low/negligible (LBD-AD=27: B0–B1) tau co-pathology and compared to age-matched AD (n=29). Hippocampal sections were stained for tau (AT8) and adjacent LBD sections stained with SYN (SYN303). Digital images of histology sections were analyzed using previously-validated methods to manually segment HIPPsf [Entorhinal Cortex (ERC), CA2/3, CA1/Subiculum and CA4/dentate gyrus(DG)] by cytoarchitectural features and measure percent area-occupied (%AO) of tau and SYN. Linear-mixed effects models and independent t-tests tested within- and between-group comparisons. Results: In the total LBD cohort, the distribution of SYN%AO was highest in CA2/3 (t=4.3, p 0.1). Tau%AO associated with SYN%AO across HIPPsf (beta=1.8, p 6.0, p Conclusions: The distribution of tau in HIPPsf in LBD correlates with SYN pathology in a relative greater distribution in CA2/3 that is distinct from AD. Disclosure: Dr. Ittyerah has nothing to disclose. Dr. Coughlin has nothing to disclose. Dr. Phillips has nothing to disclose. Dr. Miller has nothing to disclose. Dr. Lee has nothing to disclose. Dr. Trojanowski has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Trojanowski may accrue revenue in the future on patents submitted by the University of Pennsylvania wherein he is co-Inventor and he received revenue from the sale of Avid to Eli Lily as co-inventor on imaging related patents submitted by the University of Pennsylvania. Dr. Weintraub has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acadia, Alkahest, CHDI Foundation, Clintrex LLS, F. Hoffmann-LaRoche Ltd and Sunovion. Dr. Weintraub has received royalty, license fees, or contractual rights payments from University of Pennsylvania. Dr. Siderowf has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Inc. Dr. Duda has nothing to disclose. Dr. Hurtig has nothing to disclose. Dr. Wolk has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merck, Jannsen, Eli Lilly and GE. Dr. Yushkevich has nothing to disclose. Dr. Grossman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GE Whitney. Dr. Grossman has received personal compensation in an editorial capacity for Neurology. Dr. Grossman has received research support from Biogen. Dr. Irwin has nothing to disclose.