Interaction between Midlife Blood Glucose and APOE Genotype Predicts Later Alzheimer's Disease Pathology

Elevated blood glucose and the apolipoprotein (APOE) ϵ4 allele have both been associated with increased dementia risk; however, the neuropathological mechanisms underlying these associations remain unclear. We examined the impact of APOE genotype and midlife blood glucose on post-mortem vascular and Alzheimer's disease (AD) neuropathology. Ninety-four participants from the Framingham Heart Study without diagnosed diabetes underwent health examination at midlife and brain autopsy at death. Histopathological measures of vascular and AD neuropathology were obtained and analyzed. Results demonstrated that, among APOE ϵ4 carriers, elevated blood glucose was associated with more severe AD pathology. There was no such relationship with vascular pathology. In a relatively healthy sample with low vascular risk burden, midlife elevated blood glucose was associated with greater AD pathology among APOE ϵ4 carriers. A better understanding of interactive effects of APOE genotype and vascular risk on neuropathology has implications for identification of individuals at risk for decline and long-term preventive treatment.