Plasma amyloid-β peptides in type 2 diabetes: a matched case-control study

Background: Plasma amyloid-β (Aβ) levels have rarely been investigated in type 2 diabetes despite its known associations with Alzheimer's disease. Objective: To compare blood plasma Aβ concentrations (Aβ₄₀ and Aβ₄₂) in cognitively normal individuals with and without type 2 diabetes. Methods: Plasma Aβ₄₀ and Aβ₄₂ were measured in 194 participants with diabetes recruited from the community-based Fremantle Diabetes Study Phase II cohort (mean age 71 years, 59 males) and 194 age-, sex-, and APOE ϵ4 allele-matched, control subjects without diabetes from the Australian Imaging, Biomarkers and Lifestyle Study using a multiplex microsphere-based immunoassay. Results: Plasma Aβ₄₀ and Aβ₄₂ were normally distributed in the controls but were bimodal in the participants with diabetes. Median Aβ₄₀ and Aβ₄₂ concentrations were significantly lower in those with type 2 diabetes (Aβ₄₀ median [inter-quartile range]: 125.0 [52.6-148.3] versus 149.3 [134.0-165.6]pg/mL; Aβ₄₂: 26.9 [14.5-38.3] versus 33.6 [28.0-38.9]pg/mL, both p<0.001) while the ratio Aβ₄₂:Aβ₄₀ was significantly higher (0.26 [0.23-0.32] versus 0.22 [0.19-0.25], p<0.001). After adjustment, participants with diabetes and plasma Aβ₄₀ levels in the low peak of the bimodal distribution were significantly more likely to have normal to high estimated glomerular filtration rates (odds ratio (95 CI): 2.40 (1.20-4.80), p 0.013) although the group with diabetes had lower renal function overall. Conclusion: Type 2 diabetes is associated with altered plasma concentrations of Aβ peptides and is an important source of variation that needs to be taken into account when considering plasma Aβ peptides as biomarkers for Alzheimer's disease.