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Abstract Details

Hippocampal tau pathology burden in Lewy body disorders
Aging, Dementia, and Behavioral Neurology
P1 - Poster Session 1 (5:30 PM-6:30 PM)
9-014

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).

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.

 

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. 
In the total LBD cohort, the distribution of SYN%AO was highest in CA2/3 (t=4.3,p<0.001); LBD+AD and LBD-AD had similar SYN%AO across HIPPsf (t=0.01p>0.1). Tau%AO associated with SYN%AO across HIPPsf (beta=1.8, p<0.01) with greatest association in CA2/3 (beta=0.04, p<0.0001). In LBD, the distribution of Tau%AO was lowest in CA4/DG (t=-3.5,p<0.001) compared to higher levels in CA2/3, ERC and CA1/Subiculum. Across HIPPsf, AD had higher Tau%AO than both LBD+AD and LBD-AD (t>6.0,p<0.001,both) and LBD+AD had higher tau%AO than LBD-AD (t=4.8,p<0.0001); however, LBD-AD had a higher ratio of Tau%AO in CA2/3 compared to CA1/Subiculum than both LBD+AD (t=3.6,p<0.001) and AD (t=4.1,p<0.001). 
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.
Authors/Disclosures

PRESENTER 		No disclosure on file
David G. Coughlin, MD (University of California San Diego) Dr. Coughlin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for M3 Global Research. The institution of Dr. Coughlin has received research support from 好色先生. The institution of Dr. Coughlin has received research support from NIA. The institution of Dr. Coughlin has received research support from NINDS.
Jeffrey S. Phillips, PhD (Penn FTD Center, Department of Neurology) No disclosure on file
Simon Miller, MD No disclosure on file
No disclosure on file
John Q. Trojanowski, MD, PhD (University of PA School of Med) Dr. Trojanowski has nothing to disclose.
Daniel Weintraub Daniel Weintraub has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Clintrex. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Scion. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Signant. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sunovion. Daniel Weintraub has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Modality.ai. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cerevel. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CuraSen. Daniel Weintraub has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Takeda. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boehringer Ingelheim. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Daniel Weintraub has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia. Daniel Weintraub has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Movement Disorder Society. The institution of Daniel Weintraub has received research support from NIH. The institution of Daniel Weintraub has received research support from Fox Foundation. The institution of Daniel Weintraub has received research support from IPMDS. Daniel Weintraub has received intellectual property interests from a discovery or technology relating to health care.
Andrew D. Siderowf, MD Dr. Siderowf has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boehringer-Ingelheim. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving as a Consultant for askbio. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving as a Consultant for capsida. Dr. Siderowf has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Parkinson Study Group. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Theravance. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Prilenia. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Wave. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurogastrix. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Prevail. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alerity. Dr. Siderowf has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Clintrex. Dr. Siderowf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Inhibikase. Dr. Siderowf has a non-compensated relationship as a Scientific Advisory Board with NeuroPacs that is relevant to AAN interests or activities.
John E. Duda, MD (Veterans Affairs Medical Center) Dr. Duda has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Nature Publishing Group. The institution of Dr. Duda has received research support from Department of Veterans Affairs. The institution of Dr. Duda has received research support from Michael J. Fox Foundation. The institution of Dr. Duda has received research support from Innervace, Incorporated. The institution of Dr. Duda has received research support from National Institutes of Health.
Howard I. Hurtig, MD (University of Pennsylvania) No disclosure on file
David A. Wolk, MD, FAAN (University of Pennsylvania) Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Functional Neuromodulation. Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GSK. The institution of Dr. Wolk has received research support from Biogen. Dr. Wolk has received publishing royalties from a publication relating to health care. Dr. Wolk has received personal compensation in the range of $5,000-$9,999 for serving as a CME speaker with Eli Lilly.
No disclosure on file
Murray Grossman, MD, FAAN (University of Pennsylvania) Dr. Grossman has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology. The institution of Dr. Grossman has received research support from NIH.
David Irwin, MD (University of Pennsylvania) The institution of Dr. Irwin has received research support from NIH. The institution of Dr. Irwin has received research support from Prevail. The institution of Dr. Irwin has received research support from Passage Bio. The institution of Dr. Irwin has received research support from Alector. The institution of Dr. Irwin has received research support from Transposon. The institution of Dr. Irwin has received research support from Denali. The institution of Dr. Irwin has received research support from Cervo Med.