Apolipoprotein E receptor pathways in Alzheimer disease

Alzheimer disease (AD) is the most common neurodegenerative disease affecting millions of patients worldwide. According to the amyloid cascade hypothesis, the formation of neurotoxic oligomers composed of amyloid‐β (Aβ) peptides is the main mechanism that causes synaptic dysfunction and, eventually, neuronal cell death in this condition. Intriguingly, apolipoprotein E (apoE), the most important genetic risk factor for sporadic AD, emerges as a key factor that contributes to many aspects of the amyloid cascade including the clearance of Aβ from brain interstitial fluid and the ability of this peptide to form neurotoxic oligomers. Central to the activity of apoE in the healthy and in the diseased brain are apoE receptors that interact with this protein to mediate its multiple cellular and systemic effects. This review describes the molecular interactions that link apoE and its cellular receptors with neuronal viability and function, and how defects in these pathways in the brain promote neurodegeneration. This article is categorized under: Models of Systems Properties and Processes > Cellular Models Biological Mechanisms > Metabolism Physiology > Mammalian Physiology in Health and Disease