期刊
NEUROLOGY
卷 78, 期 1, 页码 55-61出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e31823ed101
关键词
-
资金
- NIH [AG025327, AG033398, P30ES007033-6364, ES004696-5897, ES012703, ES016873, NS057567, NS060252, P50NS062684, NS065070, P50NS072187]
- Department of Veterans Affairs [1I01BX000531]
- Canadian Institutes of Health Research
- Michael Smith Foundation for Health Research
- Pacific Alzheimer Research Foundation
- Canada Research Chairs program
- Mayo Clinic Florida Research Committee
- Research Committee of CNS Degenerative Diseases
- Ministry of Health, Labour and Welfare of Japan
- Lundbeck Inc.
- Allergan, Inc.
- NIH/NINDS
- Pacific Alzheimer Research Foundation (Canada)
- CIHR
- NIH
- NIH (NINDS/NIA)
- US Department of Veterans Affairs
- Parkinson's Disease Foundation
- American Parkinson Disease Association
- NIH/NIND
- Michael J. Fox Foundation
- Washington Chapter American Parkinson's Disease Association/Northwest Collaborative Care
- Centers for Disease Control
Objective: The goal of the current investigation was to examine a cohort of symptomatic and asymptomatic LRRK2 mutation carriers, in order to address whether the reported alterations in amyloid beta (A beta) and tau species in the CSF of patients with sporadic Parkinson disease (PD) are a part of PD pathogenesis, the aging process, or a comorbid disease in patients with PD, and to explore the possibility of A beta and tau as markers of early or presymptomatic PD. Methods: CSF A beta 42, total tau, and phosphorylated tau were measured with Luminex assays in 26 LRRK2 mutation carriers, who were either asymptomatic (n = 18) or had a phenotype resembling sporadic PD (n = 8). All patients also underwent PET scans with F-18-6-fluoro-L-dopa (FD), C-11-(+/-)-alpha-dihydrotetrabenazine (DTBZ), and C-11-d-threo-methylphenidate (MP) to measure dopaminergic function in the striatum. The levels of CSF markers were then compared to each PET measurement. Results: Reduced CSF A beta 42 and tau levels correlated with lower striatal dopaminergic function as determined by all 3 PET tracers, with a significant association between A beta 42 and FD uptake. When cases were restricted to carriers of the G2019S mutation, the most common LRRK2 variant in our cohort, significant correlations were also observed for tau. Conclusions: The disposition of A beta and tau is likely important in both LRRK2-related and sporadic PD, even during early phases of the disease. A better understanding of their production, aggregation, and degradation, including changes in their CSF levels, may provide insights into the pathogenesis of PD and the potential utility of these proteins as biomarkers. Neurology (R) 2012;78:55-61
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据