APOE2 orchestrated differences in transcriptomic and lipidomic profiles of postmortem AD brain.
Iliya LefterovCody M WolfeNicholas F FitzKyong Nyon NamFlorent LetronneRichard J BiedrzyckiJulia KoflerXianlin HanJianing WangJonathan SchugRadosveta KoldamovaPublished in: Alzheimer's research & therapy (2019)
The results of this study, despite the advanced stage of AD, point to the significant differences in postmortem brain transcriptomes and lipidomes, suggesting APOE allele associated differences in pathogenic mechanisms. Correlations within and between lipidomes and transcriptomes indicate coordinated effects of changes in the proteasomal system and autophagy-canonical and selective, facilitating intracellular degradation, protein entry into ER, response to ER stress, nucleolar modifications of mRNA, and likely myelination in APOEε2/c brains. Additional research and a better knowledge of the molecular mechanisms of proteostasis in the early stages of AD are required to develop more effective diagnostic approaches and eventually efficient therapeutic strategies.