Plasma β-amyloid in cognitively normal people with or without type 2 diabetes: A matched case-control study — ASN Events
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Plasma β-amyloid in cognitively normal people with or without type 2 diabetes: A matched case-control study (#73)

Kirsten E Peters 1 , Kevin Taddei 2 , Wendy A Davis 1 , Ralph N Martins 2 , Timothy ME Davis 1 , David G Bruce 1
  1. School of Medicine and Pharmacology, University of Western Australia, Fremantle, WA, Australia
  2. School of Medical Sciences, Edith Cowan University, Joondalup, WA, Australia

Plasma β-amyloid (Aβ) levels are decreased in Alzheimer’s disease (AD) and cerebral microvascular disease. Type 2 diabetes (T2D) is associated with an increased risk of dementia due to both AD and cerebrovascular disease, but whether diabetes itself modifies circulating Aβ levels is unknown. The aim of the present study was to compare circulating Aβ peptide concentrations (Aβ40 and Aβ42) in age and sex-matched individuals with and without diabetes, all of whom were cognitively normal (Mini-Mental State Examination (MMSE) score ≥27).

Plasma Aβ40 and Aβ42 were measured in 194 participants with T2D from the Fremantle Diabetes Study Phase II and 194 age- and sex-matched control subjects without diabetes from a separate general population study. Aβ peptides were measured via a multiplex microsphere-based immunoassay using Luminex xMAP technology in the same laboratory.

The patients with T2D and the non-diabetic controls had a mean age of 71 years and 59% were male. The T2D patients had a median diabetes duration of 17.4 years. Aβ40 and Aβ42 were both normally distributed in the controls and had a biphasic distribution in T2D. The ratio Aβ40:Aβ42 was unimodal in both groups. Plasma Aβ40 and Aβ42 concentrations and their ratio were significantly different in T2D patients vs non-diabetic controls (median [inter-quartile range] 125.0 [52.6-148.3] vs 149.3 [134.0-165.6] pg/mL, 26.9 [14.5-38.3] vs 33.6 [28.0-38.9] pg/mL, and 0.26 [0.23-0.32] vs 0.22 [0.19-0.25], respectively, P<0.001 by Mann-Whitney U test). In T2D, the biphasic Aβ40 distribution had a node at 80 pg/mL with 43.3% below this cut-point, and there was an equivalent node at 22 pg/mL for Aβ42 with 42.8% below this cut-point. Individuals with a low Aβ40 also had low Aβ42 concentrations with a significant association between these two measures in the T2D group as a whole (rs=0.84, P<0.001).

These findings suggest that T2D itself may alter the metabolism of circulating Aβ concentrations, an important consideration in analysing the results of studies of cognitive impairment in which Aβ concentrations are measured. The clinical and prognostic significance of the incidental finding of bimodal Aβ distributions in the patients with T2D is unknown but merits further consideration in longitudinal studies.