Wei Jiang, Martin J. Kalsbeek, Felipe Correa-da-Silva, Han Jiao, Andries Kalsbeek, Dick F. Swaab, Sarah E. Siegelaar, Chun-Xia Yi
{"title":"1型或2型糖尿病患者Meynert基底核的神经病理改变。","authors":"Wei Jiang, Martin J. Kalsbeek, Felipe Correa-da-Silva, Han Jiao, Andries Kalsbeek, Dick F. Swaab, Sarah E. Siegelaar, Chun-Xia Yi","doi":"10.1007/s00401-025-02942-y","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":7012,"journal":{"name":"Acta Neuropathologica","volume":"150 1","pages":""},"PeriodicalIF":9.3000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479689/pdf/","citationCount":"0","resultStr":"{\"title\":\"Neuropathological changes in the nucleus basalis of Meynert in people with type 1 or type 2 diabetes mellitus\",\"authors\":\"Wei Jiang, Martin J. Kalsbeek, Felipe Correa-da-Silva, Han Jiao, Andries Kalsbeek, Dick F. Swaab, Sarah E. Siegelaar, Chun-Xia Yi\",\"doi\":\"10.1007/s00401-025-02942-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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.</p></div>\",\"PeriodicalId\":7012,\"journal\":{\"name\":\"Acta Neuropathologica\",\"volume\":\"150 1\",\"pages\":\"\"},\"PeriodicalIF\":9.3000,\"publicationDate\":\"2025-09-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479689/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Neuropathologica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s00401-025-02942-y\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Neuropathologica","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s00401-025-02942-y","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
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.
期刊介绍:
Acta Neuropathologica publishes top-quality papers on the pathology of neurological diseases and experimental studies on molecular and cellular mechanisms using in vitro and in vivo models, ideally validated by analysis of human tissues. The journal accepts Original Papers, Review Articles, Case Reports, and Scientific Correspondence (Letters). Manuscripts must adhere to ethical standards, including review by appropriate ethics committees for human studies and compliance with principles of laboratory animal care for animal experiments. Failure to comply may result in rejection of the manuscript, and authors are responsible for ensuring accuracy and adherence to these requirements.