Reduced Blood Choline in Obesity Is Associated with Metabolic and Alzheimer's Biomarkers

Rising obesity rates pose significant concerns for aging and brain health. Insulin resistance (IR), prevalent in both obesity and Alzheimer's disease (AD), accelerates neurodegeneration. Adequate choline intake may help reduce obesity risk and IR, yet many individuals consume less than recommended-a deficiency associated with increased AD risk. Here, we examined circulating blood choline, metabolic dysfunction markers, inflammatory cytokines, and neurofilament light (NfL), a protein that is used as a prognostic marker for neuronal damage, in young-adult participants (mean age 33.6 years) with obesity (BMI > 30) versus healthy BMI (18.5-24.9) controls using a cross-sectional design. We also validated whether circulating choline levels correlate with NfL in a cohort of patients with mild cognitive impairment (MCI) with presence of either sparse or high neuritic plaque density and Braak stage and a second cohort with either moderate AD (moderate to frequent neuritic plaques, Braak stage = IV) or severe AD (frequent neuritic plaques, Braak stage = VI), compared to age-matched controls. We found that obese participants showed reduced circulating choline, correlating with higher %Body Fat, liver dysfunction markers, increased IR, and elevated inflammatory cytokines. NfL levels were elevated in obese participants and negatively correlated with circulating choline levels, findings consistent with that observed in MCI and AD cases. These findings reveal correlations between obesity, low choline, IR, systemic inflammation and NfL-key AD risk markers. Monitoring such markers in early adulthood may be useful for assessing future AD risk in individuals prone to obesity.