α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson's disease

被引:284
作者
Arlehamn, Cecilia S. Lindestam [1 ]
Dhanwani, Rekha [1 ]
Pham, John [1 ]
Kuan, Rebecca [1 ]
Frazier, April [1 ]
Dutra, Juliana Rezende [2 ]
Phillips, Elizabeth [3 ,4 ]
Mallal, Simon [3 ,4 ]
Roederer, Mario [5 ]
Marder, Karen S. [2 ]
Amara, Amy W. [6 ]
Standaert, David G. [6 ]
Goldman, Jennifer G. [7 ]
Litvan, Irene [8 ]
Peters, Bjoern [1 ,9 ]
Sulzer, David [10 ,11 ,12 ,13 ]
Sette, Alessandro [1 ,9 ]
机构
[1] La Jolla Inst Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA
[2] Columbia Univ, Dept Neurol, Med Ctr, Columbia, NY 10032 USA
[3] Vanderbilt Univ, Sch Med, Nashville, TN 37235 USA
[4] Murdoch Univ, Inst Immunol & Infect Dis, Perth, WA 6150, Australia
[5] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
[6] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35233 USA
[7] Northwestern Univ, Feinberg Sch Med, Shirley Ryan AbilityLab, Chicago, IL 60611 USA
[8] Univ Calif San Diego, Dept Neurol, La Jolla, CA 92093 USA
[9] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
[10] Columbia Univ, Dept Neurol, New York, NY 10032 USA
[11] Columbia Univ, Dept Psychiat, New York, NY 10032 USA
[12] Columbia Univ, Dept Pharmacol, New York, NY 10032 USA
[13] New York State Psychiat Inst & Hosp, New York, NY 10032 USA
关键词
C VIRUS-INFECTION; ALZHEIMERS-DISEASE; DIAGNOSIS;
D O I
10.1038/s41467-020-15626-w
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A diagnosis of motor Parkinson's disease (PD) is preceded by a prolonged premotor phase with accumulating neuronal damage. Here we examined the temporal relation between alpha -synuclein (alpha -syn) T cell reactivity and PD. A longitudinal case study revealed that elevated alpha -syn-specific T cell responses were detected prior to the diagnosis of motor PD, and declined after. The relationship between T cell reactivity and early PD in two independent cohorts showed that alpha -syn-specific T cell responses were highest shortly after diagnosis of motor PD and then decreased. Additional analysis revealed significant association of alpha -syn-specific T cell responses with age and lower levodopa equivalent dose. These results confirm the presence of alpha -syn-reactive T cells in PD and show that they are most abundant immediately after diagnosis of motor PD. These cells may be present years before the diagnosis of motor PD, suggesting avenues of investigation into PD pathogenesis and potential early diagnosis. alpha -Synuclein-specific T cell reactivity is preferentially associated with Parkinson's disease (PD) patients, but the temporal relation with diagnosis was previously unknown. This study reveals that alpha -syn-reactive T cells are highest before and shortly after diagnosis of motor PD, and then decrease.
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页数:11
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