Downregulation of SNX27 expression does not exacerbate amyloidogenesis in the APP/PS1 Alzheimer's disease mouse model

Neurobiology of Aging
Michael R MilneElizabeth J Coulson

Abstract

There is in vitro evidence that sorting nexin family member 27 (SNX27), a member of the retromer complex, changes the distribution of the amyloid-beta (Aβ) precursor protein (APP) to promote its recycling and thereby prevent the production of Aβ, the toxic protein associated with Alzheimer's disease (AD). In this study, we analyzed the phenotype of the familial AD APP/PS mouse strain lacking one copy of the SNX27 gene. The reduction in SNX27 expression had no significant effect on the in vivo accumulation of soluble, total, or plaque-deposited Aβ, which is overproduced by the familial APP/PS transgenes. Hippocampal structure and cholinergic basal forebrain neuronal health were also unaffected. Nonetheless, mild positive and negative effects of age and/or genotype on spatial navigation performance were observed in SNX27+/- and SNX27+/-APP/PS mice, respectively. These data suggest that downregulation of SNX27 alone does not have long-term negative consequences on spatial memory, but that cognitive dysfunction in the context of high Aβ deposition is exacerbated by the cellular or molecular changes induced by reduced SNX27 function.

Citations

May 2, 2021·Molecular Neurobiology·Neide VieiraNuno Sousa
May 4, 2021·Frontiers in Cell and Developmental Biology·Mintu ChandraLauren P Jackson

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