Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (5): 1995-1996.doi: 10.4103/NRR.NRR-D-25-00281

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Brain insulin resistance and neuropsychiatric symptoms in Alzheimer’s disease: A role for dopamine signaling

Anastasia Kontogianni, Hongbin Yang* , Wenqiang Chen*   

  1. King’s College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK (Kontogianni A) Department of Affiliated Mental Health Center of Hangzhou Seventh People’s Hospital, Liangzhu Laboratory, The State Key Lab of Brain-Machine Intelligence, Zhejiang University, Hangzhou, Zhejiang Province, China (Yang H) MOE Frontier Science Center for Brain Science & Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China (Yang H) NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, Zhejiang Province, China (Yang H) Steno Diabetes Center Copenhagen, Herlev, Denmark (Chen W) Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA (Chen W)
  • Online:2026-05-15 Published:2025-08-22
  • Contact: Hongbin Yang, PhD, hongbinyang@zju.edu.cn; Wenqiang Chen, PhD, wenqiang.chen@joslin.harvard.edu.
  • Supported by:
    This work was supported by grants from NIH T32 (DK007260, to WC), the Steno North American Fellowship awarded by the Novo Nordisk Foundation (NNF23OC0087108, to WC), STI2030-Major Projects (2021ZD0202700, to HY), the National Natural Science Foundation of China (32241004, to HY), the Natural Science Foundation of Zhejiang Province of China (LR24C090001, to HY), Key R&D Program of Zhejiang Province (2024SSYS0017, to HY), CAMS Innovation Fund for Medical Sciences (2019-12M-5-057, to HY), Fundamental Research Funds for the Central Universities (226-2022-00193, to HY), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2023-PT310-01, to HY).

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Abstract: Type 2 diabetes mellitus has central complications: Diabetes, a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion, or impaired insulin signaling, has significant central complications. Type 2 diabetes mellitus (T2DM), the most prevalent type of diabetes, affects more than 38 million individuals in the United States (approximately 1 in 10) and is defined by chronic hyperglycemia and insulin resistance, which refers to a reduced cellular response to insulin. While T2DM is commonly associated with peripheral complications, it also contributes to central complications, including neuropsychiatric symptoms (NPS) and cognitive decline (Chen et al., 2022), significantly accelerating the progression to Alzheimer’s disease (AD) and related dementias. At the core of these effects lies brain insulin resistance (BIR), a disruption in insulin signaling within the central nervous system that can occur even in individuals without diabetes (Chen et al., 2022).