ArticleAnnals of neurology2017
Brain microvascular injury and white matter disease provoked by diabetes-associated hyperamylinemia.
Article in Annals of neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 77 citations in OpenAlex.
- Amyloid-Forming Amylin Secreted by the Pancreas Promotes Hypoxia-Inducible Factor Activation and Mitochondrial Alterations in Liver and Heart During Type 2 Diabetes Pathogenesis.Comprehensive physiology · 2026Article
- Early-Onset Dementia Risk Escalates with Diabetes Duration: Insights from a Nationwide Cohort Study.Endocrinology and metabolism (Seoul, Korea) · 2026Article
- Physiological Implications of Pancreatic Amyloid Polypeptide Aggregation and Its Inhibition by Melatonin.International journal of molecular sciences · 2026Review
- Peripheral amylin modulation rebalances brain glycolysis and Tau-Ser214 phosphorylation via cAMP-PKA signaling.iScience · 2026Article
- Pancreatic hypersecretion of amyloid-forming human amylin dysregulates the neuro-immune axis and B cell development in a model of type-2 diabetes.Neurobiology of disease · 2025Article
- Amide proton transfer imaging reveals cerebral metabolic alterations associated with cognitive impairment in type 2 diabetes mellitus.Journal of translational medicine · 2025Article
- Amylin exacerbates tau pathology in the visual cortex of diabetic mice by impairing lysosomal activity.Genes & diseases · 2025Article
- Cardiac remodelling, recognition memory deficits and accelerated ageing in a rat model of gestational diabetes.Diabetologia · 2025Article
- Adaptive Immune Dyshomeostasis as a Mediator of Vascular Cognitive Decline: Unraveling Neurovascular Crosstalk.Aging and disease · 2025Review
- The role of amylin, a gut-brain axis hormone, in metabolic and neurological disorders.FASEB bioAdvances · 2025Review
- Relationship between Alzheimer's Disease and Type 2 Diabetes: Critical Review On Cellular and Molecular Common Pathogenic Mechanisms.Current Alzheimer research · 2025Review
- Automatic diagnosis of type 2 diabetes mellitus with mild cognitive impairment using artificial intelligence based on routine T1-weighted MRI.Frontiers in neurology · 2025Article
- Impact of diabetes on the association between serum urate levels and incident dementia: a cohort study in the UK biobank.The journal of nutrition, health & aging · 2024Article
- 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
- IAPP - oligomerisation levels in plasma of people with type 2 diabetes.Scientific reports · 2024Article
- Neuroinflammation induced by amyloid-forming pancreatic amylin: Rationale for a mechanistic hypothesis.Biophysical chemistry · 2024Review
- Type-2 Diabetes, Pancreatic Amylin, and Neuronal Metabolic Remodeling in Alzheimer's Disease.Molecular nutrition & food research · 2024Review
- The Contribution of Type 2 Diabetes to Parkinson's Disease Aetiology.International journal of molecular sciences · 2024Review
- The role of neurovascular coupling dysfunction in cognitive decline of diabetes patients.Frontiers in neuroscience · 2024Review
- A human antibody against pathologic IAPP aggregates protects beta cells in type 2 diabetes models.Nature communications · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveThe brain blood vessels of patients with type 2 diabetes and dementia have deposition of amylin, an amyloidogenic hormone cosecreted with insulin. It is not known whether vascular amylin deposition is a consequence or a trigger of vascular injury. We tested the hypothesis that the vascular amylin deposits cause endothelial dysfunction and microvascular injury and are modulated by amylin transport in the brain via plasma apolipoproteins.
methodsRats overexpressing amyloidogenic (human) amylin in the pancreas (HIP rats) and amylin knockout (AKO) rats intravenously infused with aggregated amylin were used for in vivo phenotyping. We also carried out biochemical analyses of human brain tissues and studied the effects of the aggregated amylin on endothelial cells ex vivo.
resultsAmylin deposition in brain blood vessels is associated with vessel wall disruption and abnormal surrounding neuropil in patients with type 2 diabetes and dementia, in HIP rats, and in AKO rats infused with aggregated amylin. HIP rats have brain microhemorrhages, white matter injury, and neurologic deficits. Vascular amylin deposition provokes loss of endothelial cell coverage and tight junctions. Intravenous infusion in AKO rats of human amylin, or combined human amylin and apolipoprotein E4, showed that amylin binds to plasma apolipoproteins. The intravenous infusion of apolipoprotein E4 exacerbated the brain accumulation of aggregated amylin and vascular pathology in HIP rats.
interpretationThese data identify vascular amylin deposition as a trigger of brain endothelial dysfunction that is modulated by plasma apolipoproteins and represents a potential therapeutic target in diabetes-associated dementia and stroke. Ann Neurol 2017;82:208-222.
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