Objective: To systematically examine the Columbia University LRRK2 brain bank for TDP-43 deposits

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. However, there are no systematic studies examining the frequency and extent of TDP-43 deposits in autopsies of patients with LRRK2 G2019S mutations.

Method: 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 threads in the substantia nigra. Clinically, all patients had parkinsonism. We did not identify a clear correlation between demographics and phenotype and TDP-43 deposits. Tau pathology was present in all brains to differing degrees.

Conclusion: TDP-43 pathology may be present in LRRK2 G2019S autopsies, at least in one case as key pathology. The implications of concomitant TDP-43 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.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/patterns-of-tdp-43-deposition-in-brains-with-lrrk2-g2019s-mutations/