Leveraging genetic propensity to identify modifiable factors for the age at onset of Alzheimer's disease

We screened 43 modifiable factors for their association with the age at onset (AAO) of Alzheimer's disease (AD) using polygenic scores (PGS) as the proxy for the exposure. Higher educational attainment, better cognitive performance, and greater relative fat intake were linked to later AAO, suggesting an enhanced resilience against AD. Type 2 diabetes, cardiovascular disease, major coronary heart disease, and increased low-density lipoprotein (LDL) -cholesterol and total cholesterol are associated with earlier AAO. Mendelian randomization analysis revealed causal effects of educational attainment, type 2 diabetes, and cardiovascular disease on AAO of AD.