Abstract
Cell Biology Three APOE alleles are expressed in humans: APOE4 allele is the single most important genetic risk factor for Alzheimer's disease, APOE3 is neutral, and APOE2 is protective. Huang et al. suggest a mechanism for the predisposing effect of APOE4 and protective effect of APOE2. APOE is normally produced by glial cells that also secrete many other factors acting on neurons. When human neurons were cultured in the absence of glial cells, APOE stimulated a MAP kinase signaling cascade in neurons, which activated amyloid-β precursor protein (APP) transcription and amyloid-β secretion. In line with their effects on Alzheimer's disease, APOE4 appeared to be more potent in stimulating APP transcription and amyloid-β secretion than APOE3, which in turn was more potent than APOE2. Cell 10.1016/j.cell.2016.12.044 (2017).
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