ArticleMolecular neurobiology2019
Mechanisms Associated with Type 2 Diabetes as a Risk Factor for Alzheimer-Related Pathology.
Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
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- Exendin-4 Prevents Memory Loss and Neuronal Death in Rats with Sporadic Alzheimer-Like Disease.Molecular neurobiology · 2024Article
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- Impairment of insulin signaling pathway PI3K/Akt/mTOR and insulin resistance induced AGEs on diabetes mellitus and neurodegenerative diseases: a perspective review.Molecular and cellular biochemistry · 2023Review
- Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System.Biomolecules · 2023Review
- The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk.Frontiers in immunology · 2023Review
- Midlife body mass index, central adiposity and neuropsychological performance over 10 years in women living with and without HIV.Frontiers in endocrinology · 2023Article
- The Metabolic Basis for Nervous System Dysfunction in Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease.Current neurovascular research · 2023Article
- Gut microbiome, cognitive function and brain structure: a multi-omics integration analysis.Translational neurodegeneration · 2022Article
- Causal association evaluation of diabetes with Alzheimer's disease and genetic analysis of antidiabetic drugs against Alzheimer's disease.Cell & bioscience · 2022Article
- Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm.Frontiers in bioscience (Landmark edition) · 2021Review
- Cognitive Impairment and Dementia: Gaining Insight through Circadian Clock Gene Pathways.Biomolecules · 2021Review
- Nicotinamide as a Foundation for Treating Neurodegenerative Disease and Metabolic Disorders.Current neurovascular research · 2021Review
- Depression as a Risk Factor for Dementia and Alzheimer's Disease.Biomedicines · 2020Article
- High fat diet worsens Alzheimer's disease-related behavioral abnormalities and neuropathology in APP/PS1 mice, but not by synergistically decreasing cerebral blood flow.Scientific reports · 2020Article
- New Insights for nicotinamide: Metabolic disease, autophagy, and mTOR.Frontiers in bioscience (Landmark edition) · 2020Review
- Dysregulation of metabolic flexibility: The impact of mTOR on autophagy in neurodegenerative disease.International review of neurobiology · 2020Review
- Ketotherapeutics for neurodegenerative diseases.International review of neurobiology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Current evidence suggests dementia and pathology in Alzheimer's Disease (AD) are both dependent and independent of amyloid processing and can be induced by multiple 'hits' on vital neuronal functions. Type 2 diabetes (T2D) poses the most important risk factor for developing AD after ageing and dysfunctional IR/PI3K/Akt signalling is a major contributor in both diseases. We developed a model of T2D, coupling subdiabetogenic doses of streptozotocin (STZ) with a human junk food (HJF) diet to more closely mimic the human condition. Over 35 weeks, this induced classic signs of T2D (hyperglycemia and insulin dysfunction) and a modest, but stable deficit in spatial recognition memory, with very little long-term modification of proteins in or associated with IR/PI3K/Akt signalling in CA1 of the hippocampus. Intracerebroventricular infusion of soluble amyloid beta 42 (Aβ42) to mimic the early preclinical rise in Aβ alone induced a more severe, but short-lasting deficits in memory and deregulation of proteins. Infusion of Aβ on the T2D phenotype exacerbated and prolonged the memory deficits over approximately 4 months, and induced more severe aberrant regulation of proteins associated with autophagy, inflammation and glucose uptake from the periphery. A mild form of environmental enrichment transiently rescued memory deficits and could reverse the regulation of some, but not all protein changes. Together, these data identify mechanisms by which T2D could create a modest dysfunctional neuronal milieu via multiple and parallel inputs that permits the development of pathological events identified in AD and memory deficits when Aβ levels are transiently effective in the brain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.