Review

Modulation of β-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family

Judy A Cam^1,2 and Guojun Bu¹

¹Departments of Pediatrics, and Cell Biology & Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA

²Department of Pathology, New York University, 550 1^st Avenue, New York, New York 10016, USA

author email corresponding author email

Molecular Neurodegeneration 2006, 1:8doi:10.1186/1750-1326-1-8

Published:	18 August 2006

Abstract

Amyloid-β peptide (Aβ) accumulation in the brain is an early, toxic event in the pathogenesis of Alzheimer's disease (AD). Aβ is produced by proteolytic processing of a transmembrane protein, β-amyloid precursor protein (APP), by β- and γ-secretases. Mounting evidence has demonstrated that alterations in APP cellular trafficking and localization directly impact its processing to Aβ. Recent studies have shown that members of the low-density lipoprotein receptor family, including LRP, LRP1B, SorLA/LR11, and apolipoprotein E (apoE) receptor 2, interact with APP and regulate its endocytic trafficking. Another common feature of these receptors is their ability to bind apoE, which exists in three isoforms in humans and the presence of the ε4 allele represents a genetic risk factor for AD. In this review, we summarize the current understanding of the function of these apoE receptors with a focus on their role in APP trafficking and processing. Knowledge of the interactions between these distinct low-density lipoprotein receptor family members and APP may ultimately influence future therapies for AD.