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bioRxiv · 10.1101/2025.01.29.635423

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

Jiang, W.·Kalsbeek, M. J.·Correa-da-Silva, F.·Kalsbeek, A.·Swaab, D. F.·Siegelaar, S. E.·Yi, C.-X.
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Abstract

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 tissues to investigate neuropathological changes. 71 postmortem NBM samples were grouped by T1DM, T2DM and non-diabetic controls, with Braak stage 0-2 or 3-6. T1DM subjects had only Braak stage 0-2 and were thus compared only to controls with a similar Braak stage and not subjects with Braak stage 3-6. We analysed neurons expressing choline acetyltransferase (ChAT), phosphorylated-Tau, glial cells and vasculature with respective markers. We found significantly less neuronal expression of ChAT in T1DM compared to controls and T2DM with Braak stage 0-2. Later-stage hyperphosphorylated-Tau levels were higher in T2DM compared to controls with Braak stages 3-6. Our results suggest that reduced acetylcholine production by NBM neurons might underlie the cognitive complains of people with T1DM. In contrast, T2DM may exacerbate neuropathological changes associated with Alzheimers disease-like alterations.

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Jiang, W., Kalsbeek, M. J., Correa-da-Silva, F., Kalsbeek, A., Swaab, D. F., Siegelaar, S. E., Yi, C.-X.. 2025-01-29. Neuropathological changes in the nucleus basalis of Meynert in people with type 1 or type 2 diabetes mellitus.. https://doi.org/10.1101/2025.01.29.635423

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