Profiling the Biochemical Signature of GBA-Related Parkinson's Disease in Peripheral Blood Mononuclear Cells

被引：29

作者：

Avenali, Micol ^{[1
,2
]}

Cerri, Silvia ^{[3
]}

Ongari, Gerardo ^{[3
,4
]}

Ghezzi, Cristina ^{[3
]}

Pacchetti, Claudio ^{[5
]}

Tassorelli, Cristina ^{[1
,2
]}

Valente, Enza Maria ^{[6
,7
]}

Blandini, Fabio ^{[2
,3
]}

机构：

[1] IRCCS Mondino Fdn, Neurorehabil Unit, Pavia, Italy

[2] Univ Pavia, Dept Brain & Behav Sci, Pavia, Italy

[3] IRCCS Mondino Fdn, Cellular & Mol Neurobiol Unit, Pavia, Italy

[4] Univ Insubria, Dept Med & Surg, Varese, Italy

[5] IRCCS Mondino Fdn, Parkinsons Dis & Movement Disorders Unit, Pavia, Italy

[6] IRCCS Mondino Fdn, Neurogenet Res Ctr, Pavia, Italy

[7] Univ Pavia, Dept Mol Med, Pavia, Italy

来源：

MOVEMENT DISORDERS | 2021年 / 36卷 / 05期

关键词：

α ‐ synuclein; glucocerebrosidase; Parkinson' s disease; exosomes; phenotyping;

D O I：

10.1002/mds.28496

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background GBA mutations are the commonest genetic risk factor for Parkinson's disease (PD) and also impact disease progression. Objective The objective of this study was to define a biochemical profile that could distinguish GBA-PD from non-mutated PD. Methods 29 GBA-PD, 37 non-mutated PD, and 40 controls were recruited; alpha-synuclein levels in plasma, exosomes, and peripheral blood mononuclear cells were analyzed, GCase and main GCase-related lysosomal proteins in peripheral blood mononuclear cells were measured. Results Assessment of plasma and exosomal alpha-synuclein levels did not allow differentiation between GBA-PD and non-mutated PD; conversely, measurements in peripheral blood mononuclear cells clearly distinguished GBA-PD from non-mutated PD, with the former group showing significantly higher alpha-synuclein levels, lower GCase activity, higher LIMP-2, and lower Saposin C levels. Conclusion We propose peripheral blood mononuclear cells as an easily accessible and manageable model to provide a distinctive biochemical profile of GBA-PD, potentially useful for patient stratification or selection in clinical trials. (c) 2021 International Parkinson and Movement Disorder Society

引用

页码：1267 / 1272

页数：6

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