Plasma Amyloid-β Peptides in Type 2 Diabetes: A Matched Case-Control Study

Background: Plasma amyloid-beta (A beta) levels have rarely been investigated in type 2 diabetes despite its known associations with Alzheimer's disease. Objective: To compare blood plasma A beta concentrations (A beta(40) and A beta(42)) in cognitively normal individuals with and without type 2 diabetes. Methods: Plasma A beta(40) and A beta(42) 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 epsilon 4 allele-matched, control subjects without diabetes from the Australian Imaging, Biomarkers and Lifestyle Study using a multiplex microsphere-based immunoassay. Results: Plasma A beta(40) and A beta(42) were normally distributed in the controls but were bimodal in the participants with diabetes. Median A beta(40) and A beta(42) concentrations were significantly lower in those with type 2 diabetes (A beta(40) median [inter-quartile range]: 125.0 [52.6-148.3] versus 149.3 [134.0-165.6] pg/mL; A beta(42): 26.9 [14.5-38.3] versus 33.6 [28.0-38.9] pg/mL, both p < 0.001) while the ratio A beta(42): A beta(4)0 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 A beta(40) 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 A beta peptides and is an important source of variation that needs to be taken into account when considering plasma A beta peptides as biomarkers for Alzheimer's disease.