Associations Between Glucose Metabolism Measures and Amyloid-β and Tau Load on PET 14 Years Later: Findings From the Framingham Heart Study.

OBJECTIVE

Type 2 diabetes and glucose metabolism have previously been linked to Alzheimer disease (AD). Yet, findings on the relation of glucose metabolism with amyloid-β and tau pathology later in life remain unclear.

RESEARCH DESIGN AND METHODS

We included 288 participants (mean age 43.1 years, SD 10.7, range 20-70 years) without dementia, from the Framingham Heart Study, who had available measures of glucose metabolism (i.e., one-time fasting plasma glucose and insulin) and positron emission tomography (PET) measures of amyloid-β and/or tau 14 years later. We performed linear regression analyses to test associations of plasma glucose (continuously and categorically; elevated defined as >100 mg/dL), plasma insulin, homeostatic model assessment for insulin resistance (HOMA-IR) with amyloid-β or tau load on PET. When significant, we explored whether age, sex, and APOE ε4 allele carriership (AD genetic risk) modified these associations.

RESULTS

Our findings indicated that elevated plasma glucose was associated with greater tau load 14 years later (B [95% CI] = 0.03 [0.01-0.05], P = 0.024 after false discovery rate [FDR] correction) but not amyloid-β. APOE ε4 carriership modified this association (B [95% CI] = -0.08 [-0.12 to -0.03], P = 0.001), indicating that the association was only present in APOE ε4 noncarriers (n = 225). Plasma insulin and HOMA-IR were not associated with amyloid-β or tau load 14 years later after FDR correction.

CONCLUSIONS

Our findings suggest that glucose metabolism is associated with increased future tau but not amyloid-β load. This provides relevant knowledge for prevention strategies and prognostics to improve health care.