Abstract Details

Title Patterns of TDP-43 Deposition in Brains with LRRK2 G2019S Mutations

Topic Movement Disorders

Presentation(s) S36 - Movement Disorders: Clinical and Pathologic Characterization of Neurodegenerative Movement Disorders (2:24 PM-2:36 PM)

Poster/Presentation
Number 008

Background LRRK2 G2019S mutations have been associated with parkinsonism and a wide range of pathological findings, including alpha-synuclein, tau and TDP-43 deposits and atrophy without clear protein aggregation (Sakuwa, 2021) (Kalia LV, 2015). However, there are no systematic studies examining the frequency and extent of TDP-43 deposits in autopsies of patients with LRRK2 G2019S mutations.

Objective

Characterize the extent of TDP-43 deposition in brains with LRRK2 G2019S mutations.

Design/Methods

There are 12 brains with LRRK2 G2019S mutations in the NY Brain Bank at Columbia University. 11 of those had samples available for TDP-43 staining, in addition to standard staining. Clinical, demographic and pathological data is reported on all cases.

Results

TDP-43 deposits were present in 8 of 11 (73%) brains in different patterns. TDP-43 threads in the amygdala were present in all positively stained brains, and among them five exclusively in the amygdala. One patient had frontotemporal lobar degeneration (FTLD) Type C with neuronal loss and gliosis primarily in the frontal lobe and aberrant TDP-43 staining mainly in the prefrontal, motor and temporal corticies. Two brains had TDP-43 staining in the substantia nigra. Tau pathology was present in all brains to differing degrees. Clinically, all patients had parkinsonism.

Conclusions TDP-43 pathology may be present in LRRK2 G2019S autopsies, at least in one case as key pathology. The implications of concomitant TDP43 deposits and PD and/or AD changes should be further explored. We recommend staining all LRRK2 autopsies for TDP-43 deposits, and genotype autopsies with predominant TDP-43 depositions for LRRK2 mutations.

Authors/Disclosures
Julian Agin-Liebes, MD (Columbia University Medical Center) PRESENTER	Dr. Agin-Liebes has nothing to disclose.
Richard Hickman	No disclosure on file
	No disclosure on file
	No disclosure on file
Richard P. Mayeux, MD, MSc, FAAN (The Neurological Institute, Columbia University Medical Center)	Dr. Mayeux has nothing to disclose.
	No disclosure on file
Karen S. Marder, MD, MPH, FAAN (Columbia University)	Dr. Marder has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Marder has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Marder has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Parkinson's Foundation . Dr. Marder has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CHDI. Dr. Marder has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC therapeutics. Dr. Marder has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer LTD. The institution of Dr. Marder has received research support from Vaccinex. The institution of Dr. Marder has received research support from Genentech. The institution of Dr. Marder has received research support from Triplet Therapeutics. The institution of Dr. Marder has received research support from Prilenia.
Roy Alcalay, MD (Columbia University)	Dr. Alcalay has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genzyme/Sanofi. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gain Therapeutics. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vanqua Bio. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Capsida. Dr. Alcalay has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Servier. The institution of Dr. Alcalay has received research support from Michael J. Fox Foundation. The institution of Dr. Alcalay has received research support from Parkinson's Foundation. The institution of Dr. Alcalay has received research support from Silverstein Foundation. Dr. Alcalay has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant with Parkinson's Foundation.