biostudies-literatureUnknown141(2)Zhao YNational Institute of Neurological Disorders and StrokeMedical Research CouncilNational Institute of Mental HealthNational Institutes of HealthMissense mutations in leucine-rich repeat kinase 2 (LRRK2) are pathogenic for familial Parkinson's disease. However, it is unknown whether levels of LRRK2 protein in the brain are altered in patients with LRRK2-associated Parkinson's disease. Because LRRK2 mutations are relatively rare, accounting for approximately 1% of all Parkinson's disease, we accessioned cases from five international brain banks to investigate levels of the LRRK2 protein, and other genetically associated Parkinson's disease proteins. Brain tissue was obtained from 17 LRRK2 mutation carriers (12 with the G2019S mutation and five with the I2020T mutation) and assayed by immunoblot. Compared to matched controls and idiopathic Parkinson's disease cases, we found levels of LRRK2 protein were reduced in the LRRK2 mutation Brain : a journal of neurology486-495https://www.ebi.ac.uk/biostudies/studies/S-EPMC5837795biostudies-literatureReduced LRRK2 in association with retromer dysfunction in post-mortem brain tissue from LRRK2 mutation carriers.PMC5837795Takahashi-Fujigasaki JUchino AMurayama SDzamko NHolton JLVonsattel JPGMash DCJeremy Nichols RZhao YPerera GHasegawa KHalliday GMfalseReduced LRRK2 in association with retromer dysfunction in post-mortem brain tissue from LRRK2 mutation carriers.Missense mutations in leucine-rich repeat kinase 2 (LRRK2) are pathogenic for familial Parkinson's disease. However, it is unknown whether levels of LRRK2 protein in the brain are altered in patients with LRRK2-associated Parkinson's disease. Because LRRK2 mutations are relatively rare, accounting for approximately 1% of all Parkinson's disease, we accessioned cases from five international brain banks to investigate levels of the LRRK2 protein, and other genetically associated Parkinson's disease proteins. Brain tissue was obtained from 17 LRRK2 mutation carriers (12 with the G2019S mutation and five with the I2020T mutation) and assayed by immunoblot. Compared to matched controls and idiopathic Parkinson's disease cases, we found levels of LRRK2 protein were reduced in the LRRK2 mutation 2018-01-01T00:00:00Z2018 Feb2025-04-18T14:01:21.796Z2019-03-26T23:06:54ZS-EPMC58377952925308610.1093/brain/awx344