DJ-1 and αSYN in LRRK2 CSF do not correlate with striatal dopaminergic function

NEUROBIOLOGY OF AGING

卷:33

Article

Shi, Min¹  Furay, Amy R.¹  Sossi, Vesna²  Aasly, Jan O.³  Armaly, Jeff¹  Wang, Yu^1,4  Wszolek, Zbigniew K.⁵  Uitti, Ryan J.⁵  Hasegawa, Kazuko⁶  Yokoyama, Teruo⁶  Zabetian, Cyrus P.^7,8,9  Leverenz, James B.^8,9,10,11  Stoessl, A. Jon^12,13  Zhang, Jing¹ 

[1] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA

[2] Univ British Columbia, Dept Phys & Astron, Vancouver Hosp & Hlth Sci Ctr, Vancouver, BC V5Z 1M9, Canada

[3] St Olavs Hosp, Dept Neurol, Trondheim, Norway

[4] Huazhong Univ Sci & Technol, Dept Neurosurg, Tongji Hosp, Tongji Med Coll, Wuhan 430074, Peoples R China

[5] Mayo Clin Florida, Dept Neurol, Jacksonville, FL USA

[6] Sagamihara Natl Hosp, Dept Neurol, Natl Hosp Org, Sagamihara, Kanagawa, Japan

[7] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA

[8] Vet Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA

[9] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA

[10] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA

[11] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA

[12] Univ British Columbia, Pacific Parkinsons Res Ctr, Vancouver, BC V5Z 1M9, Canada

[13] Vancouver Coastal Hlth, Vancouver, BC, Canada

关键词: Parkinson's disease;    LRRK2;    Gene mutation;    Biomarker;    DJ-1;    alpha-synuclein;   

DOI  :  10.1016/j.neurobiolaging.2011.09.015

来源: Elsevier

【 摘 要 】

Previous studies demonstrated decreased levels of DJ-1 and alpha-synuclein (alpha SYN) in human cerebrospinal fluid (CSF) in patients with Parkinson's disease (PD), but neither marker correlated with PD severity, raising the possibility that they may be excellent progression markers during early or preclinical phases of PD. Individuals carrying the leucine-rich repeat kinase 2 (LRRK2) gene mutation are at increased risk for PD, and the phenotype of LRRK2 patients is almost identical to sporadic PD. To determine whether dopaminergic dysfunction in the basal ganglia, as determined by positron emission tomography (PET) scans, correlates with CSF levels of DJ-1 and alpha SYN during preclinical stages, Luminex assays were used to analyze CSF samples from asymptomatic LRRK2 mutation carriers, along with carriers who presented with a clinical diagnosis of PD. The data revealed no statistically significant relationship between PET scan evidence of loss of striatal dopaminergic function and the CSF biomarkers DJ-1 and alpha SYN, except for a weak correlation between DJ-1 and methylphenidate binding, suggesting that the use of these potential biomarkers on their own to screen LRRK2 gene mutation carriers for PD is not appropriate. (C) 2012 Elsevier Inc. All rights reserved.

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