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Nat Rev Neurosci. 2009 May;10(5):333-44. doi: 10.1038/nrn2620. Epub 2009 Apr 2.

Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy.

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Hope Center for Neurological Disorders, Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA.


The vast majority of Alzheimer's disease (AD) cases are late-onset and their development is probably influenced by both genetic and environmental risk factors. A strong genetic risk factor for late-onset AD is the presence of the epsilon4 allele of the apolipoprotein E (APOE) gene, which encodes a protein with crucial roles in cholesterol metabolism. There is mounting evidence that APOE4 contributes to AD pathogenesis by modulating the metabolism and aggregation of amyloid-beta peptide and by directly regulating brain lipid metabolism and synaptic functions through APOE receptors. Emerging knowledge of the contribution of APOE to the pathophysiology of AD presents new opportunities for AD therapy.

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