Modulation of amyloid β-protein clearance and Alzheimer's disease susceptibility by the LDL receptor-related protein pathway

被引：313
作者：
Kang, DE
Pietrzik, CU
Baum, L
Chevallier, N
Merriam, DE
Kounnas, MZ
Wagner, SL
Troncoso, JC
Kawas, CH
Katzman, R
Koo, EH [1 ]
机构：
[1] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA
[2] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Kowloon, Hong Kong, Peoples R China
[3] Neurogenet Inc, San Diego, CA USA
[4] Johns Hopkins Univ, Sch Med, Dept Neurol, Alzheimers Dis Res Ctr, Baltimore, MD 21205 USA
[5] Johns Hopkins Univ, Sch Med, Dept Pathol Neuropathol & Neurol, Alzheimers Dis Res Ctr, Baltimore, MD 21205 USA
来源：
JOURNAL OF CLINICAL INVESTIGATION | 2000年 / 106卷 / 09期
关键词：
D O I：
10.1172/JCI11013
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Susceptibility to Alzheimer's disease (AD) is governed by multiple genetic factors. Remarkably, the LDL receptor-related protein (LRP) and its ligands, apoE and alpha 2M, are all genetically associated with AD. In this study, we provide evidence for the involvement of the LRP pathway in amyloid deposition through sequestration and removal of soluble amyloid beta -protein (A beta). We demonstrate in vitro that LRP mediates the clearance of both A beta 40 and A beta 42 through a bona fide receptor-mediated uptake mechanism. In vivo, reduced LRP expression is associated with LRP genotypes and is correlated with enhanced soluble A beta levels and amyloid deposition. Although LRP has been proposed to be a clearance pathway for A beta, this work provides the first in vivo evidence that the LRP pathway may modulate A beta deposition and AD susceptibility by regulating the removal of soluble A beta.
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收藏
页码：1159 / 1166
页数：8
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