title: LRRK2 I2020T mutation is associated with tau pathology.
abstract: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of autosomal-dominant familial Parkinson's disease (FPD). The variable pathological features of LRRK2-linked FPD include Lewy bodies, degeneration of anterior horn cells associated with axonal spheroids, neurofibrillary tangles (NFTs) and TAR DNA-binding protein of 43 kDa (TDP-43) positive inclusion bodies. Furthermore, abnormal hyperphosphorylation of microtubule associated protein tau, in part generated by catalysis of protein kinases, has been reported to be involved in progressive neurodegeneration in a number of diseases, including FPD. Thus, we examined six patients carrying the LRRK2 I2020T mutation, a pathogenic mutation associated with PARK8, and found abnormal tau phosphorylation depositions in the brainstem. Additionally, we found LRRK2 I2020T enhanced tau phosphorylation in cultured cells co-expressing LRRK2-I2020T and 3 or 4-repeated tau. This is the first report describing the relationship between hyperphosphorylation of tau and LRRK2 I2020T.
authors.affiliation: Department of Neurology, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ujiie
authors.forename: Taku
authors.initials: T
authors.lastname: Hatano
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Kubo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Imai
authors.forename: Shigeto
authors.initials: S
authors.lastname: Sato
authors.forename: Toshiki
authors.initials: T
authors.lastname: Uchihara
authors.forename: Saburo
authors.initials: S
authors.lastname: Yagishita
authors.forename: Kazuko
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Kowa
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sakai
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
mesh_terms: D001933:Brain Stem / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases