The effects of gender on the relationship between body mass index and CSF AB42 and tau levels

Overweight and obesity are associated with increased risk for Alzheimer's disease (AD), but the mechanisms through which increased body mass index (BMI) affects AD risk are not known. To describe the relationship between BMI and cerebrospinal fluid (CSF) markers of AD progression, namely CSF Aβ42 and tau levels, in a group of middle-aged adults at increased risk for AD. Fifty cognitively-healthy middle-aged adult children of persons with AD were recruited from the Wisconsin Registry for Alzheimer's Prevention (WRAP) (mean age± SD 53.5± 6.7 {range 42–69} years, 37 women). CSF and blood samples and measures of blood pressure, weight, and height were obtained in all subjects. CSF Aβ42 and tau levels were measured by ELISA and fasting blood lipoprotein levels by NMR spectroscopy. Mean± SD BMI in participants was 28.0± 6.1 kg/m2 (range 19–48 kg/m2). CSF Aβ42 and tau levels and the following components of the metabolic syndrome were similar in men and women (all p>0.1): BMI, systolic blood pressure, total and low-density lipoprotein (LDL) cholesterol, and triglyceride values. Women had greater high-density lipoprotein (HDL) cholesterol levels than men (67.1± 17.9 vs. 45.3± 7.8 mg/dL, p<0.001). Men tended to have higher fasting glucose levels than women (96.7± 7.8 vs. 91.1± 9.3 mg/dL, p=0.057). Only one subject had self-reported diabetes mellitus. In men, BMI showed a strong inverse correlation with CSF Aβ42 (r= -0.719, p=0.006) and tau (r= -0.679, p=0.011, see figure). No significant relationship was noted between BMI and CSF biomarkers in women (see figure). Controlling for components of the metabolic syndrome did not alter the relationship between BMI and CSF biomarkers. Increased BMI is associated with lower CSF Aβ42 and tau levels in middle-aged men at risk for AD, but not in women. As lower CSF Aβ42 levels may predict risk of future cognitive decline, these findings suggest that increased BMI may contribute to the pathobiology of AD progression in men. As men tend to have more atherogenic central adiposity, these data strengthen evidence supporting a relationship between vascular risk and AD.