Nicholas Fitz

Research to characterize the Alzheimer’s Disease Exposome will address major gaps in understanding of how environmental factors interact with genetic factors to increase or reduce risk for the disease across individual age and duration of exposure. This research direction in AD is now supported by recent articles published by the Alzheimer’s Association and funding through the NIA. We know that increasing age is the most important risk factor for Alzheimer’s disease, but many other risk factors including environmental exposures are poorly understood. The importance of environmental factors in gene-environment interactions is suggested by wide individual differences in cognitive loss and pathology progression, particularly among people who carry genes that increase the risk of Alzheimer’s disease. Among carriers of APOE4, few people never develop the disease – suggesting environmental risk as contributing to that variability. A recent study showed that environmental factors including exposure to air pollution and low socioeconomic status shifted the onset by ten years in a cohort of familial Alzheimer’s disease patients. The proposed AD exposome includes macrolevel external factors such as living in rural versus urban areas, along with individual external factors such as toxicant exposures, diet, exercise and infections. These exogenous domains can overlap and interact with endogenous factors including individual fat deposits, hormones, and brain injury. One could assume that some of these endogenous factors cold result in system interactions, describing a “lung-brain axis” for inhaled neurotoxicants of air pollution and cigarette smoke, or a “renal-brain axis” for renal aging driven by diet and hypertension. To further develop an Alzheimer’s disease “roadmap” of modifiable factors in brain aging and dementia, we are exploring how the exposome, with low level arsenic exposure as a model, impacts the normal function of neurons, microglia and astrocytes through assessing changes in the cell specific epigenome, homeostatic functions, and lipid transport. We hypothesis that exposures, either during important developmental windows or during long periods of one’s life, will influence normal neural functions which could predispose to AD or accelerate the disease progression. I have a broad background in the use of transgenic animal models, transcriptomics, microscopy, molecular genetics, cellular and molecular biology, with specific training and expertise in molecular pathogenesis and experimental therapy for neurodegenerative disease and neuroinflammation.