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Interaction of insulin hormone with neurotransmitters in the pathogenesis of Alzheimer's disease
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Sam Torabi Goodarzi1   , Issa Layali2  , Zahra Nematollah3 |
1- Independent researcher
2- , Department of Biochemistry and Biophysics, TeMS.C., Islamic Azad University, Tehran, Iran , drissalayali@gmail.com
3- Master's Student in Biochemistry, TeMS.C., Islamic Azad University, Tehran, Iran |
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Abstract: (5 Views) |
Background: The association between insulin resistance and Alzheimer's disease (AD) has been proposed as the "type 3 diabetes" hypothesis. This systematic review investigates the role of impaired cerebral insulin signaling in the pathogenesis of AD and its therapeutic prospects.
Materials and methods: Following the PRISMA guidelines, a comprehensive search was conducted in PubMed/MEDLINE, Scopus, and Web of Science databases up to 2025. After screening, 32 studies were included in the review.
Results: Cerebral insulin resistance is a key pathological factor in AD that acts through independent mechanisms. It impairs amyloid-beta (Aβ) clearance by reducing the activity of insulin-degrading enzyme (IDE) and by disrupting the PI3K/Akt pathway, leads to GSK-3β activation and tau hyperphosphorylation. These processes, together with impaired neurotransmission and inflammation, form a vicious cycle of neurodegeneration and support the concept of type 3 diabetes. In contrast, emerging therapies such as intranasal insulin and GLP-1 agonists have shown potential to improve molecular markers and cognition in early studies.
Conclusion: Cerebral insulin resistance is an important and targetable causal component in the pathogenesis of AD. Targeting this pathway is a promising therapeutic strategy. However, challenges such as standardization of measurement, rigorous trial design, and crossing the blood-brain barrier require attention before widespread clinical application. Future research should focus on identifying biomarkers and developing combination therapies.
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| Keywords: Insulin hormone, Alzheimer’s diseaseو Amyloid-beta, Neuroplasticity |
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Full-Text [PDF 711 kb]
(2 Downloads)
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Semi-pilot: Review |
Subject:
Cilinical Biochemistry
Received: 2025/12/15 | Accepted: 2026/02/22 | Published: 2026/09/1
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