Peripheral inflammation and APOE - its role on microglia in Alzheimer’s Disease

Alzheimer’s disease is related with a progressive loss of brain function, is one of the main causes of dementia, and affects more than 50 million people worldwide. Among the factors influencing Alzheimer’s disease occurrence, the genetic expression of APOE4 is one of the highest risk factors for the development of late-onset Alzheimer’s disease. There is a certain predisposition for women to be more affected by Alzheimer’s disease, but also environmental factors and early life infections increase the chances of suffering cognitive impairment. Neuroinflammation is a relevant component of Alzheimer’s disease together with the cerebral expression of amyloid-β plaques and neurofibrillary tangles. APOE4 is closely related to neuroinflammation, affecting the normal functioning of microglial cells, but the molecular mechanisms through which it exerts its negative effects are yet not fully understood. Therefore, this project aims to study the influence of sex, early-life stress and the APOE genotype in the neuroinflammatory microglial responses and Alzheimer’s disease pathological features, as well as the peripheral immune response and the molecular mechanisms implicated. Results retrieved from this study will potentially lead to the development of more effective Alzheimer's disease therapies.