Biomarkers of insulin resistance, oxidative stress, and nutrition and the brain

McLimans, Kelsey
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Alzheimer’s disease (AD) is a neurological disorder that has been linked with nutrition and lifestyle choices throughout the lifespan. Although there is currently no cure, recent research supports dietary changes as a preventative measure for AD. However, it is not clear which nutritional markers underlie the structural and functional changes in the brain that are seen in AD, and subsequently what aspect of the diet should be targeted in AD prevention and treatment. The projects described in this dissertation provide four nutritional biomarkers that are associated with AD pathology: the metabolism-regulating enzyme autotaxin, the insulin transporter and modifier insulin-like growth factor binding protein 2, the antioxidant superoxide dismutase 1, and the micronutrient involved in methylation of proteins and lipids as well as homocysteine metabolism, vitamin B12. These studies analyze neurological associations through region of interest approaches, voxel-wise analyses, and statistical analyses (i.e. linear mixed models, mediation models, logistic regression) with established cerebrospinal fluid (CSF) biomarkers of AD, cognitive test scores, and baseline and follow-up diagnoses. Our findings suggest that CSF autotaxin is detrimental to brain health and superoxide dismutase 1 is most likely beneficial. Insulin-like growth factor binding protein is suggested to be beneficial early in the AD trajectory, but detrimental as the disease progresses. Lastly, our results suggest that higher serum vitamin B12 may be indicative of worse AD outcomes in an aged population but contrastingly better cognitive associations in a young population. Future studies are needed to determine causation as well as the impact of nutritional modifications on these biomarkers and subsequent brain health.

Alzheimer's Disease, Metabolic Disorders, Neuroimaging, Reactive Oxygen Species