| First Author | Nuriel T | Year | 2017 |
| Journal | Front Neurosci | Volume | 11 |
| Pages | 702 | PubMed ID | 29311783 |
| Mgi Jnum | J:276755 | Mgi Id | MGI:6307614 |
| Doi | 10.3389/fnins.2017.00702 | Citation | Nuriel T, et al. (2017) The Endosomal-Lysosomal Pathway Is Dysregulated by APOE4 Expression in Vivo. Front Neurosci 11:702 |
| abstractText | Possession of the epsilon4 allele of apolipoprotein E (APOE) is the major genetic risk factor for late-onset Alzheimer's disease (AD). Although numerous hypotheses have been proposed, the precise cause of this increased AD risk is not yet known. In order to gain a more comprehensive understanding of APOE4's role in AD, we performed RNA-sequencing on an AD-vulnerable vs. an AD-resistant brain region from aged APOE targeted replacement mice. This transcriptomics analysis revealed a significant enrichment of genes involved in endosomal-lysosomal processing, suggesting an APOE4-specific endosomal-lysosomal pathway dysregulation in the brains of APOE4 mice. Further analysis revealed clear differences in the morphology of endosomal-lysosomal compartments, including an age-dependent increase in the number and size of early endosomes in APOE4 mice. These findings directly link the APOE4 genotype to endosomal-lysosomal dysregulation in an in vivo, AD pathology-free setting, which may play a causative role in the increased incidence of AD among APOE4 carriers. |
