ArticleJournal of Alzheimer's disease : JAD2016
Intraneuronal Amylin Deposition, Peroxidative Membrane Injury and Increased IL-1β Synthesis in Brains of Alzheimer's Disease Patients with Type-2 Diabetes and in Diabetic HIP Rats.
Article in Journal of Alzheimer's disease : JAD, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 65 citations in OpenAlex.
- Peripheral amylin modulation rebalances brain glycolysis and Tau-Ser214 phosphorylation via cAMP-PKA signaling.iScience · 2026Article
- Anti-diabetic drug pioglitazone reduces Islet amyloid aggregation overload in the Drosophila neuronal cells.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Type 2 Diabetes Mellitus: A Metabolic Model of Accelerated Aging - Multi-Organ Mechanisms and Intervention Approaches.Aging and disease · 2025Review
- Comparison of Methods of Detecting IL-1β in the Blood of Alzheimer's Disease Subjects.International journal of molecular sciences · 2025Article
- Alzheimer's Disease, Obesity, and Type 2 Diabetes: Focus on Common Neuroglial Dysfunctions (Critical Review and New Data on Human Brain and Models).Brain sciences · 2024Review
- Type-2 Diabetes, Pancreatic Amylin, and Neuronal Metabolic Remodeling in Alzheimer's Disease.Molecular nutrition & food research · 2024Review
- Neuroinflammation induced by amyloid-forming pancreatic amylin: Rationale for a mechanistic hypothesis.Biophysical chemistry · 2024Review
- The Contribution of Type 2 Diabetes to Parkinson's Disease Aetiology.International journal of molecular sciences · 2024Review
- A pancreatic player in dementia: pathological role for islet amyloid polypeptide accumulation in the brain.Neural regeneration research · 2023Review
- Mitochondria and Oxidative Stress as a Link between Alzheimer's Disease and Diabetes Mellitus.International journal of molecular sciences · 2023Review
- Comment on Yoo et al. Amylin Protein Expression in the Rat Brain and Neuro-2a Cells.International journal of molecular sciences · 2023Article
- Aβ efflux impairment and inflammation linked to cerebrovascular accumulation of amyloid-forming amylin secreted from pancreas.Communications biology · 2023Article
- The association between renal accumulation of pancreatic amyloid-forming amylin and renal hypoxia.Frontiers in endocrinology · 2023Review
- Alzheimer's Disease as Type 3 Diabetes: Common Pathophysiological Mechanisms between Alzheimer's Disease and Type 2 Diabetes.International journal of molecular sciences · 2022Review
- Beyond CGRP: The calcitonin peptide family as targets for migraine and pain.British journal of pharmacology · 2022Review
- Bloodborne Pancreatic Amylin, a Therapeutic Target for Alzheimer's Disease.Current Alzheimer research · 2022Review
- Amylin Pharmacology in Alzheimer's Disease Pathogenesis and Treatment.Current neuropharmacology · 2022Review
- Rosmarinic Acid Potently Detoxifies Amylin Amyloid and Ameliorates Diabetic Pathology in a Transgenic Rat Model of Type 2 Diabetes.ACS pharmacology & translational science · 2021Article
- Amylin Dyshomeostasis Hypothesis: Small Vessel-Type Ischemic Stroke in the Setting of Type-2 Diabetes.Stroke · 2021Review
- Amylin antibodies frequently display cross-reactivity with CGRP: characterization of eight amylin antibodies.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Amylin is a hormone synthesized and co-secreted with insulin by pancreatic β-cells that crosses the blood-brain barrier and regulates satiety. Amylin from humans (but not rodents) has an increased propensity to aggregate into pancreatic islet amyloid deposits that contribute to β-cell mass depletion and development of type-2 diabetes by inducing oxidative stress and inflammation. Recent studies demonstrated that aggregated amylin also accumulates in brains of Alzheimer's disease (AD) patients, preponderantly those with type-2 diabetes. Here, we report that, in addition to amylin plaques and mixed amylin-Aβ deposits, brains of diabetic patients with AD show amylin immunoreactive deposits inside the neurons. Neuronal amylin formed adducts with 4-hydroxynonenal (4-HNE), a marker of peroxidative membrane injury, and increased synthesis of the proinflammatory cytokine interleukin (IL)-1β. These pathological changes were mirrored in rats expressing human amylin in pancreatic islets (HIP rats) and mice intravenously injected with aggregated human amylin, but not in hyperglycemic rats secreting wild-type non-amyloidogenic rat amylin. In cultured primary hippocampal rat neurons, aggregated amylin increased IL-1β synthesis via membrane destabilization and subsequent generation of 4-HNE. These effects were blocked by membrane stabilizers and lipid peroxidation inhibitors. Thus, elevated circulating levels of aggregated amylin negatively affect the neurons causing peroxidative membrane injury and aberrant inflammatory responses independent of other confounding factors of diabetes. The present results are consistent with the pathological role of aggregated amylin in the pancreas, demonstrate a novel contributing mechanism to neurodegeneration, and suggest a direct, potentially treatable link of type-2 diabetes with AD.
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Registered trials
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