Endosomal-Lysosomal and Autophagy Pathway in Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Autor: Saffire H. Krance, Che-Yuan Wu, Alison C.Y. Chan, Stephanie Kwong, Bing Xin Song, Lisa Y. Xiong, Michael Ouk, Ming Hui Chen, Jane Zhang, Adrian Yung, Meagan Stanley, Nathan Herrmann, Krista L. Lanctôt, Walter Swardfager
Rok vydání: 2022
Předmět:
Zdroj: Journal of Alzheimer's Disease. 88:1279-1292
ISSN: 1875-8908
1387-2877
DOI: 10.3233/jad-220360
Popis: Background: The endosomal-lysosomal and autophagy (ELA) pathway may be implicated in the progression of Alzheimer’s disease (AD); however, findings thus far have been inconsistent. Objective: To systematically summarize differences in endosomal-lysosomal and autophagy proteins in the cerebrospinal fluid (CSF) of people with AD and healthy controls (HC). Methods: Studies measuring CSF concentrations of relevant proteins in the ELA pathway in AD and healthy controls were included. Standardized mean differences (SMD) with 95% confidence intervals (CI) between AD and healthy controls in CSF concentrations of relevant proteins were meta-analyzed using random-effects models. Results: Of 2,471 unique studies, 43 studies were included in the systematic review and meta-analysis. Differences in ELA protein levels in the CSF between AD and healthy controls were observed, particularly in lysosomal membrane (LAMP-1: NAD/NHC = 348/381, SMD [95% CI] = 0.599 [0.268, 0.930], I2 = 72.8%; LAMP-2: NAD/NHC = 401/510, SMD [95% CI] = 0.480 [0.134, 0.826], I2 = 78.7%) and intra-lysosomal proteins (GM2A: NAD/NHC = 390/420, SMD [95% CI] = 0.496 [0.039, 0.954], I2 = 87.7%; CTSB: NAD/NHC = 485/443, SMD [95% CI] = 0.201 [0.029, 0.374], I2 = 28.5%; CTSZ: NAD/NHC = 535/820, SMD [95% CI] = –0.160 [–0.305, –0.015], I2 = 24.0%) and in proteins involved in endocytosis (AP2B1:NAD/NHC = 171/205, SMD [95% CI] = 0.513 [0.259, 0.768], I2 = 27.4%; FLOT1: NAD/NHC = 41/45, SMD [95% CI] = –0.489 [–0.919, –0.058], I2
Databáze: OpenAIRE
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