Extracellular vesicle proteome unveils cathepsin B connection to Alzheimer's disease pathogenesis

被引：14

作者：

Yuyama, Kohei ^{[1
]}

Sun, Hui ^{[1
]}

Fujii, Risa ^{[2
]}

Hemmi, Isao ^{[3
]}

Ueda, Koji ^{[2
]}

Igeta, Yukifusa ^{[4
,5
]}

机构：

[1] Hokkaido Univ, Fac Adv Life Sci, Lipid Biofunct Sect, Sapporo 0010021, Japan

[2] Japanese Fdn Canc Res, Canc Precis Med Ctr, Canc Prote Grp, Tokyo 0358550, Japan

[3] Japanese Red Cross Coll Nursing, Dept Nursing, Tokyo 1500012, Japan

[4] Toranomon Gen Hosp, Dementia Ctr, Dept Dementia, Tokyo 1058470, Japan

[5] Okinaka Mem Inst Med Res, Div Dementia Res, Tokyo 1058470, Japan

来源：

BRAIN | 2024年 / 147卷 / 02期

基金：

日本学术振兴会;

关键词：

extracellular vesicle; Alzheimer's disease; ATN classification; cathepsin B; blood biomarker; AMYLOID-BETA; EXOSOMES; BRAIN; INHIBITION; HYPOTHESIS; DIAGNOSIS; PATHWAY; MODEL;

D O I：

10.1093/brain/awad361

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Extracellular vesicles (EVs) are membrane vesicles that are released extracellularly and considered to be implicated in the pathogenesis of neurodegenerative diseases including Alzheimer's disease. Here, CSF EVs of 16 ATN-classified cases were subjected to quantitative proteome analysis. In these CSF EVs, levels of 11 proteins were significantly altered during the ATN stage transitions (P < 0.05 and fold-change > 2.0). These proteins were thought to be associated with Alzheimer's disease pathogenesis and represent candidate biomarkers for pathogenic stage classification. Enzyme-linked immunosorbent assay analysis of CSF and plasma EVs revealed altered levels of cathepsin B (CatB) during the ATN transition (seven ATN groups in validation set, n = 136). The CSF and plasma EV CatB levels showed a negative correlation with CSF amyloid-beta(42) concentrations. This proteomic landscape of CSF EVs in ATN classifications can depict the molecular framework of Alzheimer's disease progression, and CatB may be considered a promising candidate biomarker and therapeutic target in Alzheimer's disease amyloid pathology.

引用

页码：627 / 636

页数：10

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