EFFECT OF GESTATIONAL HIGH FAT DIET ON ALZHEIMER’S DISEASE SUSCEPTIBILITY IN THE OFFSPRING

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting over five million people in the US alone. Causes for the most common sporadic form of the disease are still obscure and no therapeutic approach is available to halt the progression of AD. Subjects whose mothers were affected by sporadic AD are three times more susceptible to develop the disease later in life compared to subject from sporadic AD fathers. However, the mechanisms of maternal transmissibility for sporadic AD are unknown. Lifestyle and nutrition are important risk factors for sporadic AD. Direct exposure to saturated fats and cholesterol is positively correlated to AD development later in life. We hypothesized that maternal exposure to high-fat diet throughout gestation would affect AD susceptibility in the offspring later in life. To tackle this biological question, triple transgenic (3xTg) dams carrying human APP (KM670/671NL), PSEN1 (M146V) and MAPT (P301L) mutations together with wild type da