The E4 allele of APOE is a major genetic risk of developing sporadic Alzheimer's disease. However, the mechanisms linking this gene variant to the development of pathological hallmarks in patients neurones remains unclear. Here, neurones and astrocytes were generated from isogenic human induced pluripotent stem cells carrying the E3 or E4 alleles to investigate the influence of APOE4 astrocytes on neuronal amyloid-beta production. The results showed that paracrine signalling of diseased astrocytes increased the production of amyloid precursor protein and secretion of amyloid-beta in neurones. Furthermore, modulation of cholesterol levels demonstrated that cholesterol secretion from APOE4 astrocytes was necessary and sufficient to induce pathological outcomes through the formation of lipid rafts. Overall, the researchers reveal key pathological mechanisms involving APOE4 astrocytes-driven oversupply of cholesterol that lead to neuronal amyloidosis.
APOE4-carrying human astrocytes oversupply cholesterol to promote neuronal lipid raft expansion and Aβ generation
The IE from MS no longer understands current scripting languages, the latest main version (version 11) is from 2013 and has not been further developed since 2015.
Our recommendation: Use only the latest versions of modern browsers, for example Google Chrome, Mozilla Firefox or Microsofrt Edge, because only this guarantees you sufficient protection against infections and the correct display of websites!