ArticleJournal of neuroinflammation2019
Time course of neuropathological events in hyperhomocysteinemic amyloid depositing mice reveals early neuroinflammatory changes that precede amyloid changes and cerebrovascular events.
Article in Journal of neuroinflammation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- TNF inhibition differentially impacts regional Abeta immunotherapy efficacy in the humanized hAbAlzheimer's research & therapy · 2026Article
- Consumption of Cashew Nuts on Oxidative Stress and Neuroinflammation Markers in Methionine-Induced Hyperhomocysteinemia in Rats.Food science & nutrition · 2026Article
- Exploring the Effects of Empagliflozin Administration and Physical Training on Cognitive Functions in an Amyloid Beta-Induced Alzheimer's Rat Model.Current medicinal chemistry · 2026Article
- Entwined processes in Alzheimer's disease: Brain cellular senescence and Alzheimer's disease pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Article
- The Role of Methionine-Rich Diet in Unhealthy Cerebrovascular and Brain Aging: Mechanisms and Implications for Cognitive Impairment.Nutrients · 2023Review
- Article
- Hypertension and hyperhomocysteinemia as modifiable risk factors for Alzheimer's disease and dementia: New evidence, potential therapeutic strategies, and biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Review
- Apolipoprotein E ε4/4 genotype limits response to dietary induction of hyperhomocysteinemia and resulting inflammatory signaling.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Genetic expression changes and pathologic findings associated with hyperhomocysteinemia in human autopsy brain tissue.Alzheimer's & dementia (New York, N. Y.) · 2022Article
- Article
- The Role of Methyl Donors of the Methionine Cycle in Gastrointestinal Infection and Inflammation.Healthcare (Basel, Switzerland) · 2021Review
- Hyperhomocysteinemia: Metabolic Role and Animal Studies with a Focus on Cognitive Performance and Decline-A Review.Biomolecules · 2021Review
- Reactive astrocytes: The nexus of pathological and clinical hallmarks of Alzheimer's disease.Ageing research reviews · 2021Review
- Homocysteine and Gliotoxicity.Neurotoxicity research · 2021Review
- Methionine Diet Evoked Hyperhomocysteinemia Causes Hippocampal Alterations, Metabolomics Plasma Changes and Behavioral Pattern in Wild Type Rats.International journal of molecular sciences · 2021Article
- Pathologic sequelae of vascular cognitive impairment and dementia sheds light on potential targets for intervention.Cerebral circulation - cognition and behavior · 2021Article
- Microglial-associated responses to comorbid amyloid pathology and hyperhomocysteinemia in an aged knock-in mouse model of Alzheimer's disease.Journal of neuroinflammation · 2020Article
- Maternal Hyperhomocysteinemia Induces Neuroinflammation and Neuronal Death in the Rat Offspring Cortex.Neurotoxicity research · 2020Article
- Effect of Methionine Diet on Time-Related Metabolic and Histopathological Changes of Rat Hippocampus in the Model of Global Brain Ischemia.Biomolecules · 2020Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundVascular contributions to cognitive impairment and dementia (VCID) are the second leading cause of dementia behind only Alzheimer's disease (AD); however, VCID is commonly found as a co-morbidity with sporadic AD. We have previously established a mouse model of VCID by inducing hyperhomocysteinemia in both wild-type and amyloid depositing mice. While we have shown the time course of neuropathological events in the wild-type mice with hyperhomocysteinemia, the effect of amyloid deposition on this time course remains unknown; therefore, in this study, we determined the time course of neuropathological changes in our mouse model of hyperhomocysteinemia-induced VCID in amyloid depositing mice.
methodsAPP/PS1 mice were placed on either a diet deficient in folate and vitamins B6 and B12 and enriched in methionine to induce hyperhomocysteinemia or a control diet for 2, 6, 10, 14, or 18 weeks. Immunohistochemistry and gene expression analysis were used to determine neuroinflammatory changes. Microhemorrhages and amyloid deposition were analyzed using histology and, finally, behavior was assessed using the 2-day radial arm water maze.
resultsNeuroinflammation, specifically a pro-inflammatory phenotype, was the first pathological change to occur. Specifically, we see a significant increase in gene expression of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, and interleukin 12a by 6 weeks. This was followed by cognitive deficits starting at 10 weeks. Finally, there is a significant increase in the number of microhemorrhages at 14 weeks on diet as well as redistribution of amyloid from the parenchyma to the vasculature.
conclusionsThe time course of these pathologies points to neuroinflammation as the initial, key player in homocysteine-induced VCID co-morbid with amyloid deposition and provides a possible therapeutic target and time points.
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