Patterns of TDP‐43 Deposition in Brains with LRRK2 G2019S Mutations

Abstract

AbstractObjectiveTo assess for TDP‐43 deposits in brains with and without a LRRK2 G2019S mutation.Background LRRK2 G2019S mutations have been associated with parkinsonism and a wide range of pathological findings. There are no systematic studies examining the frequency and extent of TDP‐43 deposits in neuropathological samples from LRRK2 G2019S carriers.MethodsTwelve brains with LRRK2 G2019S mutations were available for study from the New York Brain Bank at Columbia University; 11 of them had samples available for TDP‐43 immunostaining. Clinical, demographic, and pathological data are reported for 11 brains with a LRRK2 G2019S mutation and compared to 11 brains without GBA1 or LRRK2 G2019S mutations with a pathologic diagnosis of Parkinson's disease (PD) or diffuse Lewy body disease. They were frequency matched by age, gender, parkinsonism age of onset, and disease duration.ResultsTDP‐43 aggregates were present in 73% (n = 8) of brains with a LRRK2 mutation and 18% (n = 2) of brains without a LRRK2 mutation (P = 0.03). In one brain with a LRRK2 mutation, TDP‐43 proteinopathy was the primary neuropathological change.ConclusionsExtranuclear TDP‐43 aggregates are observed with greater frequency in LRRK2 G2019S autopsies compared to PD cases without a LRRK2 G2019S mutation. The association between LRRK2 and TDP‐43 should be further explored. © 2023 International Parkinson and Movement Disorder Society.