Abstract：
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.
To systematically summarize differences in endosomal-lysosomal and autophagy proteins in the cerebrospinal fluid (CSF) of people with AD and healthy controls (HC).
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.
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 <0.01). LC3B, an autophagy marker, also showed a difference (NAD/NHC = 70/59, SMD [95% CI] = 0.648 [0.180, 1.116], I2 = 38.3%)), but overall there was limited evidence suggesting differences in proteins involved in endosomal function and autophagy.
Dysregulation of proteins in the ELA pathway may play an important role in AD pathogenesis. Some proteins within this pathway may be potential biomarkers for AD.
To systematically summarize differences in endosomal-lysosomal and autophagy proteins in the cerebrospinal fluid (CSF) of people with AD and healthy controls (HC).
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.
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 <0.01). LC3B, an autophagy marker, also showed a difference (NAD/NHC = 70/59, SMD [95% CI] = 0.648 [0.180, 1.116], I2 = 38.3%)), but overall there was limited evidence suggesting differences in proteins involved in endosomal function and autophagy.
Dysregulation of proteins in the ELA pathway may play an important role in AD pathogenesis. Some proteins within this pathway may be potential biomarkers for AD.
摘要：
内体-溶酶体和自噬（ELA）途径可能与阿尔茨海默病（AD）的进展有关；然而，到目前为止，调查结果并不一致。
系统总结AD患者和健康对照者（HC）脑脊液（CSF）内体-溶酶体和自噬蛋白的差异。
包括测量AD和健康对照中ELA途径中相关蛋白的CSF浓度的研究。使用随机效应模型，对AD和健康对照之间CSF相关蛋白浓度的标准化平均差异（SMD）和95％置信区间（CI）进行荟萃分析。
在2,471项独特研究中,43项研究纳入系统评价和荟萃分析。观察到AD和健康对照之间CSF中ELA蛋白水平的差异，特别是在溶酶体膜中（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％）和溶酶体内蛋白（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％）和参与内吞作用的蛋白质（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<0.01)。LC3B,自噬标记,也显示出差异(NAD/NHC=70/59，SMD[95%CI]=0.648[0.180，1.116]，I2=38.3%))，但总体而言，有限的证据表明参与内体功能和自噬的蛋白质存在差异。
ELA途径中蛋白质的失调可能在AD发病机制中起重要作用。该途径中的一些蛋白质可能是AD的潜在生物标志物。
系统总结AD患者和健康对照者（HC）脑脊液（CSF）内体-溶酶体和自噬蛋白的差异。
包括测量AD和健康对照中ELA途径中相关蛋白的CSF浓度的研究。使用随机效应模型，对AD和健康对照之间CSF相关蛋白浓度的标准化平均差异（SMD）和95％置信区间（CI）进行荟萃分析。
在2,471项独特研究中,43项研究纳入系统评价和荟萃分析。观察到AD和健康对照之间CSF中ELA蛋白水平的差异，特别是在溶酶体膜中（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％）和溶酶体内蛋白（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％）和参与内吞作用的蛋白质（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<0.01)。LC3B,自噬标记,也显示出差异(NAD/NHC=70/59，SMD[95%CI]=0.648[0.180，1.116]，I2=38.3%))，但总体而言，有限的证据表明参与内体功能和自噬的蛋白质存在差异。
ELA途径中蛋白质的失调可能在AD发病机制中起重要作用。该途径中的一些蛋白质可能是AD的潜在生物标志物。
