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The Endosomal-Lysosomal Pathway Is Dysregulated by APOE4 Expression in Vivo
Ist Teil von
Frontiers in neuroscience, 2017-12, Vol.11, p.702-702
Ort / Verlag
Switzerland: Frontiers Research Foundation
Erscheinungsjahr
2017
Quelle
EZB Free E-Journals
Beschreibungen/Notizen
Possession of the ε4 allele of apolipoprotein E (
) 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
'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
-specific endosomal-lysosomal pathway dysregulation in the brains of
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
mice. These findings directly link the
genotype to endosomal-lysosomal dysregulation in an
, AD pathology-free setting, which may play a causative role in the increased incidence of AD among
carriers.