Metabolic dysfunction worsens cognition and neuronal resilience in a rat model of early Alzheimer

MARTINO-ADAMI, PAMELA VICTORIA; GALEANO, PABLO; WALLINGER, MARINA LAURA; RABOSSI, ALEJANDRO; RADI, RAFAEL; GEVORKIAN, GOAR; CUELLO, AUGUSTO CLAUDIO; MORELLI, LAURA

Córdoba

Congreso; 52 Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2016

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Alzheimer's disease (AD) is the leading cause of dementia in older adults and represents a serious medical, social and economic problem. Although diet is a modifiable risk factor for AD, the mechanisms linking peripheral metabolism and cognition remain unclear. To address this question, we have chosen McGill-R-Thy1-APP transgenic rats (Tg(+/-)) that mimic presymptomatic AD pathology. Wild-type and Tg(+/-) rats were exposed from 35 days to 6 months of age to a standard diet or a Western diet (WD), high in saturated fat and sugar. Our results of peripheral and hippocampal biochemical analysis show that WD induced a metabolic syndrome and decreased presynaptic bioenergetic parameters. Furthermore, cognitive tests, ELISA multiplex, Western blot, immunohistochemistry and quantitative RT-PCR results indicate that WD worsened cognition, increased hippocampal levels of oligomeric and monomeric ABeta species (38/40/42), promoted deposits of N-terminal pyroglutamate-ABeta in CA1 pyramidal neurons and interneurons, reduced neuronal resilience and increased nitrated proteins in Tg(+/-) rats. Our results support the concept that diet-induced metabolic dysfunction may contribute as a second hit to impair cognition in the presence of early ABeta pathology, reinforcing the relevance of optimizing fat and sugar consumption for the prevention of AD, at least in people with genetic risk factors.