Aim: We aimed to elucidate the dynamics of blood biomarkers according to the severity of cognitive impairment in patients with type 2 diabetes mellitus (DM) and to identify useful biomarkers for diabetes-related dementia.
Methods: This was a cross-sectional, nested case-control study of 121 Japanese DM and non-DM patients with different levels of cognitive functioning. We evaluated participants' cognitive functions, blood biomarkers related to Alzheimer's disease, and soluble triggering receptors expressed on myeloid cells 2 (sTREM2). We then compared these biomarkers between the DM and non-DM and across the different cognitive strata.
Results: In all cognitive strata, significantly lower levels of serum sTREM2 were observed in the DM than in the non-DM. We also found that plasma levels of phosphorylated tau (p-tau) increased with increasing levels of cognitive decline in both the DM and non-DM. However, this was accompanied by a decrease in plasma amyloid-β(Aβ42/Aβ40 ratios in non-DM only.
Conclusion: This study revealed novel characteristic trajectories of dementia-related blood biomarkers in diabetes-related dementia, suggesting the pathological involvement of molecular cascades initiated by impaired microglial activation. This results in decreased serum sTREM2, followed by tauopathy without substantial amyloid plaques, reflected by plasma p-tau elevation with no decrease in the Aβ42/Aβ40 ratio. Clinical trials (the unique trial number and the name of the registry): UMIN000048032, https://www.umin.ac.jp.
Keywords: Aβ42/Aβ40 ratio; Blood biomarkers; Diabetes-related dementia; Serum soluble TREM2; Type 2 diabetes mellitus.
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