ArticleMolecular neurodegeneration2022
Islet amyloid polypeptide cross-seeds tau and drives the neurofibrillary pathology in Alzheimer's disease.
Article in Molecular neurodegeneration, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Shaping the future of preclinical development of successful disease-modifying drugs against Alzheimer's disease: a systematic review of tau propagation models.Acta neuropathologica communications · 2024Pooled it
- Brain insulin resistance as a driver of proteinopathy in neurodegeneration: from cell-type-specific mechanisms to targeted therapeutics.Translational neurodegeneration · 2026Review
- From Molecular Networks to Medicines: Targeting Complexity in Alzheimer's Disease (AD) Therapy.Molecular neurobiology · 2026Review
- TNMD BRICHOS domain attenuates tau pathology and memory deficits in a mouse model of tauopathy.Cell death & disease · 2026Article
- Resveratrol modulates pancreatic proteotoxic stress and metabolic dysfunction in human IAPP transgenic mice.Frontiers in endocrinology · 2026Article
- From seeds to symptoms: the molecular landscape of tau seeding in Alzheimer's disease.Frontiers in neuroscience · 2026Review
- Evaluation of distinct and similar pathological features between diabetes and Alzheimer's disease.EXCLI journal · 2026Review
- Micro- and Nanoplastics and Functional Nutrients in Human Health: Epigenetic Mechanisms and Cellular Resilience Signaling in Brain Insulin Resistance and the Risk of Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Amylin exacerbates tau pathology in the visual cortex of diabetic mice by impairing lysosomal activity.Genes & diseases · 2025Article
- Human amylin is a potent antimicrobial peptide that exhibits antimicrobial synergism with the amyloid beta protein.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Article
- Experimental methods for studying amyloid cross-interactions.Protein science : a publication of the Protein Society · 2025Review
- Comparative efficacy and safety of antidiabetic agents in Alzheimer's disease: A network meta-analysis of randomized controlled trials.The journal of prevention of Alzheimer's disease · 2025Article
- Article
- Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus.Open medicine (Warsaw, Poland) · 2025Review
- Alzheimer's Disease as Type 3 Diabetes: Understanding the Link and Implications.International journal of molecular sciences · 2024Review
- Mechanism of Metal Complexes in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Brain Microvascular Pericyte Pathology Linking Alzheimer's Disease to Diabetes.Microcirculation (New York, N.Y. : 1994) · 2024Review
- Tau in neurodegenerative diseases: molecular mechanisms, biomarkers, and therapeutic strategies.Translational neurodegeneration · 2024Review
- PM2.5 triggers tau aggregation in a mouse model of tauopathy.JCI insight · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe pathologic accumulation and aggregation of tau is a hallmark of tauopathies including Alzheimer's disease (AD). However, the molecular mechanisms mediating tau aggregation in AD remain elusive. The incidence of AD is increased in patients with type 2 diabetes (T2DM), which is characterized by the amyloid deposition of islet amyloid polypeptide (IAPP) in the pancreas. However, the molecular mechanisms bridging AD and T2DM remain unknown.
methodsWe first examined the presence of IAPP in the neurofibrillary tangles of AD patients. Then we tested the effect of IAPP on tau aggregation. The biochemical and biological characteristics of the IAPP-tau fibrils were tested in vitro. The seeding activity and neurotoxicity of the IAPP-tau fibrils were confirmed in cultured neurons. Lastly, the effect of IAPP on tau pathology and cognitive impairments was determined by injecting the IAPP-tau fibrils and IAPP fibrils into the hippocampus of tau P301S mice.
resultsWe found that IAPP interacts with tau and accelerates the formation of a more toxic strain, which shows distinct morphology with enhanced seeding activity and neurotoxicity in vitro. Intrahippocampal injection of the IAPP-tau strain into the tau P301S transgenic mice substantially promoted the spreading of tau pathology and induced more severe synapse loss and cognitive deficits, when compared with tau fibrils. Furthermore, intracerebral injection of synthetic IAPP fibrils initiated tauopathy in the brain of tau P301S transgenic mice.
conclusionsThese observations indicate that IAPP acts as a crucial mediator of tau pathology in AD, and provide a mechanistic explanation for the higher risk of AD in individuals with T2DM.
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