HDL mimetic peptides affect apolipoprotein E metabolism: equal supplement or functional enhancer?: An Editorial for 'High-density lipoprotein mimetic peptide 4F mitigates amyloid-β-induced inhibition of apolipoprotein E secretion and lipidation in primary astrocytes and microglia' on page 647.

ε4 allele of ApoE is the strongest genetic risk factor for late onset Alzheimer's disease (AD). Supplementation of ApoE proteins or mimetics has been pursued for drug developments against AD. A very low-density lipoprotein (HDL) mimetic peptide 4F was shown to alleviate AD-related deficits in APP transgenic mice, and this editorial highlights a study by Chernick et al. who use both mouse and human neuroglial cells to explore the mechanism underlying beneficial effects of this peptide. The authors demonstrate that 4F peptide significantly increased the secretion and lipidation of ApoE in the absence and presence of Aβ independent of de novo transcription/translation, but requiring ABCA1 and the integrity of the secretory pathway between ER and Golgi. This study reveals a novel mechanism of HDL mimetic peptide as a functional ApoE enhancer and support further development of ApoA-I 4F peptide as effective ApoE modulating agents against AD.