Human apolipoprotein E (ApoE) isoforms among which ApoE4, constitute the most important genetic risk factor for Alzheimer's disease (AD). Up to know, how ApoE isoforms influence Alzheimer pathogenesis remains unclear. Recently, using ES-cell-derived human neurons, the team of the Nobel Prize, Thomas Sudhof (Standford, USA) demonstrated that ApoE secreted by glia binds to ApoE receptors, stimulates the transcription factor AP-1, which in turn enhances neuronal transcription of amyloid-β precursor protein (APP) and thereby increases amyloid-β levels. The amyloid-β peptides are the main component of the amyloid deposits that progressively accumulate in the brain of Alzheimer patients. In this recent article in Cell journal in January 2017, Sudhof’s team describes then a novel signal transduction pathway both in vitro and in vivo, whereby ApoE activates APP transcription and amyloid-β synthesis.
More details in Huang et al. 2017, ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and Aβ Secretion. Cell. 168(3):427-441. Click here
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