| Autor: |
Tal Nuriel, Katherine Y. Peng, Archana Ashok, Allissa A. Dillman, Helen Y. Figueroa, Justin Apuzzo, Jayanth Ambat, Efrat Levy, Mark R. Cookson, Paul M. Mathews, Karen E. Duff |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Frontiers in Neuroscience, Vol 11 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
1662-453X |
| DOI: |
10.3389/fnins.2017.00702 |
| Popis: |
Possession of the ε4 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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