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LRRK2 I2020T mutation is associated with tau pathology.
MedLine Citation:
PMID:  22525366     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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:
Sachiko Ujiie; Taku Hatano; Shin-Ichiro Kubo; Satoshi Imai; Shigeto Sato; Toshiki Uchihara; Saburo Yagishita; Kazuko Hasegawa; Hisayuki Kowa; Fumihiko Sakai; Nobutaka Hattori
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-21
Journal Detail:
Title:  Parkinsonism & related disorders     Volume:  -     ISSN:  1873-5126     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9513583     Medline TA:  Parkinsonism Relat Disord     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Neurology, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Department of Neurology, Kitasato University, School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0329, Japan.
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