Abstract Details

Title Coincident Alzheimer’s disease modifies alpha-synuclein pathology in Lewy body disease

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) (-)

Poster/Presentation
Number 005

Objective

Background Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common, frequently co-ocurring, neurodegenerative diseases. Dementia with Lewy Bodies (DLB) is defined by dementia with fluctuating cognitive symptoms and the appearance of a parkinsonian syndrome >1 year after dementia onset. Staging systems have been proposed for tau and A? deposits in AD as well as for alpha-synuclein pathology (ASP) in PD and DLB although no consensus has been reached.

Design/Methods We studied the distribution of ASP in DLB subjects with coincident AD (AD+DLB, n=313) and compared it to the distribution in PD cases without AD (PD, n=134) and with AD (PD+AD, n=71) from the University of Pennsylvania (UPenn) and the Banner Sun Health Research Institute. Cases were classified by ASP distribution into amygdala predominant, brainstem predominant, limbic (with/ without brainstem involvement) and neocortical using a modified Unified Staging System for Lewy Body Disorders scheme. Dopamine transporter immunohistochemistry was performed on a subset of the UPenn cohort.

Results The amygdala predominant ASP category was present in AD+DLB cases and not PD cases. The limbic category presented a lower burden of brainstem, subcortical and frontal ASP in the DLB cases compared to the PD cases. In the neocortical category, PD only cases showed a lower burden of temporal and angular cortex ASP than the PD+AD and the DLB only cases. PD and PD+AD groups in the UPenn cohort showed a higher burden of ASP in the substantia nigra compared to the DLB only group. The nigro-striatal pathway, defined by dopamine transporter immunohistochemistry, was relatively preserved in the DLB+AD groups compared to the PD only and PD+AD groups.

Conclusions The presence of AD pathology modifies the burden and distribution of ASP in the alpha-synucleinopathies studied here.

Authors/Disclosures
Jon B. Toledo	No disclosure on file
	No disclosure on file
	No disclosure on file
Erin Abner	No disclosure on file
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.
Johannes Brettschneider, MD (University of Ulm, Neurology)	No disclosure on file
Steven E. Arnold, MD (Massachusetts General Hospital)	Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EIP Pharma. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sage Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cortexyme. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Boyle Shaughnessy Law. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Wolf Greenfield. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board Member with Bob's Last Marathon.
Howard I. Hurtig, MD (University of Pennsylvania)	No disclosure on file
Peter T. Nelson	Peter T. Nelson has nothing to disclose.
Charles H. Adler, MD, PhD, FAAN (Mayo Clinic Arizona)	Dr. Adler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal. Dr. Adler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avion. Dr. Adler has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CND Life Sci. Dr. Adler has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Jazz. Dr. Adler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Precon. Dr. Adler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurocrine. The institution of Dr. Adler has received research support from NIH. The institution of Dr. Adler has received research support from Michael J. Fox Foundation. The institution of Dr. Adler has received research support from Arizona Biomedical Research Commission. Dr. Adler has received publishing royalties from a publication relating to health care.
Thomas Beach (Banner Sun Health Research Institute)	Thomas Beach has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vivid Genomics. Thomas Beach has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche Diagnostics. The institution of Thomas Beach has received research support from National Institutes of Health. The institution of Thomas Beach has received research support from Michael J Fox Foundation . The institution of Thomas Beach has received research support from State of Arizona.
John Q. Trojanowski, MD, PhD (University of PA School of Med)	Dr. Trojanowski has nothing to disclose.

��ɫ��

��ɫ��