METABOLIC DYSFUNCTION WORSENS COGNITION AND NEURONAL RESILIENCE IN A RAT MODEL OF EARLY ALZHEIMER

MARTINO ADAMI PV; GALEANO P; WALLINGER ML; RABOSSI A; RADI R; GEVORKIAN G; CUELLO C; MORELLI L

Cordoba

Congreso; SAIB - 5 2 th Annual Meeting Argentine Society for Biochemistry and Molecular Biology L I I Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2016

SAIB

Alzheimer's disease (AD) is the leading cause ofdementia in older adults and represents a serious medical, social and economicproblem. Although diet is a modifiable risk factor for AD, the mechanismslinking peripheral metabolism and cognition remain unclear. To address thisquestion, we have chosen McGill-R-Thy1-APP transgenic rats (Tg(+/-)) that mimicpresymptomatic AD pathology. Wild-type and Tg(+/-) rats were exposed from 35days to 6 months of age to a standard diet or a Western diet (WD), high insaturated fat and sugar. Our results of peripheral and hippocampal biochemicalanalysis show that WD induced a metabolic syndrome and decreased presynapticbioenergetic parameters. Furthermore, cognitive tests, ELISAmultiplex, Western blot, immunohistochemistry and quantitative RT-PCR results indicatethat WD worsened cognition, increased hippocampal levels of oligomeric and monomericAβ species (38/40/42), promoted deposits of N-term pyroglutamate-Aβ in CA1 neurons,reduced neuronal resilience and increased nitrated proteins in Tg(+/-) rats. Ourresults support the concept that diet-induced metabolic dysfunctions maycontribute as a ?second hit? to impair cognition in the presence of early Aβpathology, reinforcing the relevance of optimizing fat and sugar consumptionfor the prevention of AD, at least in people with genetic risk factors.