Increased midlife triglycerides predict brain -amyloid and tau pathology 20 years later

ObjectiveTo evaluate the effect of midlife lipid levels on Alzheimer brain pathology 20 years later in cognitively normal elderly individuals.MethodsThis is a longitudinal cohort study of 318 cognitively normal individuals with data on fasting lipid levels at midlife (mean age 54 years). Presence of -amyloid (A) and tau pathologies 20 years later (mean age 73 years) were detected by quantifying Alzheimer disease (AD) biomarkers in CSF. In a subset (n = 134), A (F-18-flutemetamol) PET was also performed.ResultsCSF A(42) and A PET revealed A pathology in approximately 20% of the cognitively healthy population and CSF A(42)/phosphorylated tau (p-tau) ratio indicated both A and tau pathology in 16%. Higher levels of triglycerides in midlife were independently associated with abnormal CSF A(42) (odds ratio [OR] 1.34, 95% confidence interval [CI] 1.03-1.75, p = 0.029) and abnormal A(42)/p-tau ratio (OR 1.46, 95% CI 1.10-1.93; p = 0.009) adjusting for age, sex, APOE epsilon 4, education, and multiple vascular risk factors. Triglycerides were also associated with abnormal A PET in multivariable regression models, but the association was attenuated in the fully adjusted model. Increased levels of medium and large low-density lipoprotein subfractions were significantly associated with abnormal A PET and large high-density lipoprotein particles were associated with decreased risk of abnormal A PET.ConclusionsIncreased levels of triglycerides at midlife predict brain A and tau pathology 20 years later in cognitively healthy individuals. Certain lipoprotein subfractions may also be risk factors for A pathology. These findings further support an involvement of lipids in the very early stages of AD development.