Evaluation of Neuropathological Effects of a High-Fat Diet in a Presymptomatic Alzheimer's Disease Stage in APP/PS1 Mice

Ettcheto, Miren; Petrov, Dmitry; Pedros, Ignacio; Alva, Norma; Carbonell, Teresa; Beas-Zarate, Carlos; Pallas, Merce; Auladell, Carme; Folch, Jaume; Camins, Antoni


Alzheimer's disease (AD) is currently an incurable aging-related neurodegenerative disorder. Recent studies give support to the hypotheses that AD should be considered as a metabolic disease. The present study aimed to explore the relationship between hippocampal neuropathological amyloid-beta (A beta) plaque formation and obesity at an early presymptomatic disease stage (3 months of age). For this purpose, we used APPswe/PS1dE9 (APP/PS1) transgenic mice, fed with a high-fat diet (HFD) in order to investigate the potential molecular mechanisms involved in both disorders. The results showed that the hippocampus from APP/PS1 mice fed with a HFD had an early significant decrease in A beta signaling pathway specifically in the insulin degrading enzyme protein levels, an enzyme involved in (A beta) metabolism, and alpha-secretase. These changes were accompanied by a significant increase in the occurrence of plaques in the hippocampus of these mice. Furthermore, APP/PS1 mice showed a significant hippocampal decrease in PGC-1 alpha levels, a cofactor involved in mitochondrial biogenesis. However, HFD does not provoke changes in neither insulin receptors gene expression nor enzymes involved in the signaling pathway. Moreover, there are no changes in any enzymes (kinases) involved in tau phosphorylation, such as CDK5, and neither in brain oxidative stress production. These results suggest that early changes in brains of APP/PS1 mice fed with a HFD are mediated by an increase inA beta(1-42), which induces a decrease in PKA levels and alterations in the p-CREB/NMDA2B/PGC1-alpha pathway, favoring early AD neuropathology in mice.

Más información

Título según WOS: ID WOS:000383838400023 Not found in local WOS DB
Volumen: 54
Número: 1
Editorial: IOS Press
Fecha de publicación: 2016
Página de inicio: 233
Página final: 251


Notas: ISI