Neuropathological changes in the nucleus basalis of Meynert in people with type 1 or type 2 diabetes mellitus

People with type 1 or type 2 diabetes mellitus (T1DM or T2DM) often experience cognitive impairment. We profiled cells in the nucleus basalis of Meynert (NBM) in postmortem human brain tissue to investigate the neuropathological changes. Sixty-eight postmortem NBM samples were grouped as T1DM, T2DM, and controls without diabetes, with Braak stage 0-II or III-VI. T1DM subjects had only Braak stage 0-II and were thus compared only to controls with a similar Braak stage and not subjects with Braak stage III-VI. We analyzed neurons expressing choline acetyltransferase (ChAT), phosphorylated tau, amyloid-beta, glial cells, and vasculature with their respective markers. We found significantly lower neuronal expression of ChAT in T1DM individuals than in controls and T2DM individuals with Braak stage 0-II. Later-stage hyperphosphorylated tau levels were higher in T2DM compared to controls with Braak stage III-VI. Our results suggest that reduced acetylcholine production by NBM neurons may underlie the cognitive complaints of people with T1DM. In contrast, T2DM may exacerbate neuropathological changes associated with Alzheimer's disease-like alterations.