biostudies-literatureWalton RLNIA NIH HHSMayo Clinic LBD Center WithOut WallsNINDS NIH HHSADRCNIHNIH HHS54https://www.ebi.ac.uk/biostudies/studies/S-EPMC11049671biostudies-literatureUnknown147(1)Rare and common GBA variants are risk factors for both Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, the degree to which GBA variants are associated with neuropathological features in Lewy body disease (LBD) is unknown. Herein, we assessed 943 LBD cases and examined associations of 15 different neuropathological outcomes with common and rare GBA variants. Neuropathological outcomes included LBD subtype, presence of a high likelihood of clinical DLB (per consensus guidelines), LB counts in five cortical regions, tyrosine hydroxylase immunoreactivity in the dorsolateral and ventromedial putamen, ventrolateral substantia nigra neuronal loss, Braak neurofibrillary tangle (NFT) stage, Thal amyloid phase, phospho-ubiquitin (pS65-Ub) level, TDP-43 pathology, and vascular Acta neuropathologicaRole of GBA variants in Lewy body disease neuropathology.PMC11049671R01 NS078086U01 NS100620U19 AG071754U54 NS110435R01 NS110085P30 AG062677P50 NS072187U54-NS110435P01 AG003949U19 AG074879UG3 NS104095R01 NS085070P50 AG016574R56 AG062556U54 NS100693P50-NS072187U19 AG063911Fiesel FCDickson DWBeasley AIJack CRHou XGraff-Radford NRBotha HParisi JEWszolek ZKSpringer WKoga SBoeve BFWalton RLGriesacker TGraff-Radford JMurray MEHeckman MGRoss OAReichard RRPetersen RCRamanan VKFerman TJUitti RJFields JAWhite LJKasanuki KLowe VJSavica RKantarci KErtekin-Taner NfalseRole of GBA variants in Lewy body disease neuropathology.Rare and common GBA variants are risk factors for both Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, the degree to which GBA variants are associated with neuropathological features in Lewy body disease (LBD) is unknown. Herein, we assessed 943 LBD cases and examined associations of 15 different neuropathological outcomes with common and rare GBA variants. Neuropathological outcomes included LBD subtype, presence of a high likelihood of clinical DLB (per consensus guidelines), LB counts in five cortical regions, tyrosine hydroxylase immunoreactivity in the dorsolateral and ventromedial putamen, ventrolateral substantia nigra neuronal loss, Braak neurofibrillary tangle (NFT) stage, Thal amyloid phase, phospho-ubiquitin (pS65-Ub) level, TDP-43 pathology, and vascular 2024-01-01T00:00:00Z2024 Mar2026-06-03T04:43:20.494Z2025-04-06T22:14:28.208ZS-EPMC110496713847244310.1007/s00401-024-02699-w