Modeling Mixed Vascular and Alzheimer ’s Dementia Using Focal Subcortical Ischemic Stroke in Human ApoE4-TR:5XFAD Transgenic Mice

AbstractSubcortical white matter ischemic lesions are increasingly recognized to have pathologic overlap in individuals with Alzheimer ’s disease (AD). The interaction of white matter ischemic lesions with amyloid pathology seen in AD is poorly characterized. We designed a novel mouse model of subcortical white matter ischemic stroke and AD that can inform our understanding of the cellular and molecular mechanisms of mixed vascul ar and AD dementia. Subcortical white matter ischemic stroke underlying forelimb motor cortex was induced by local stereotactic injection of an irreversible eNOS inhibitor. Subcortical white matter ischemic stroke or sham procedures were performed on human ApoE4-targeted-replacement (TR):5XFAD mice at 8 weeks of age. Behavioral tests were done at 7, 10, 15, and 20 weeks. A subset of animals underwent18FDG-PET/CT. At 20  weeks of age, brain tissue was examined for amyloid plaque accumulation and cellular changes. Compared with sham E4-TR:5XFAD mice, those with an early subcortical ischemic stroke showed a significant reduction in amyloid plaque burden in the region of cortex overlying the subcortical stroke. Cogni tive performance was improved in E4-TR:5XFAD mice with stroke compared with sham E4-TR:5XFAD animals. Iba-1+ microglial cells in the region of cortex overlying the subcortical stroke were increased in number and morphologic complexity compared with sham E4-TR:5XFAD mice, suggesting that amyloid clea rance may be promoted...
Source: Translational Stroke Research - Category: Neurology Source Type: research

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(Bentham Science Publishers) There is a considerable overlap between vascular risk factors and risk factors of Alzheimer's disease (AD). In addition, incident stroke approximately doubles the risk of developing AD. Oxidative stress is significantly involved in the pathogenesis of AD and suffers a dramatic increase in the setting of acute ischemic stroke, especially in cardioembolic stroke, followed by lacunar stroke. Dampening this oxidative burst could delay the onset of subsequent dementia in stroke survivors.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Abstract The significant gain in life expectancy led to an increase in the incidence and prevalence of dementia. Although vascular risk factors have long and repeatedly been shown to increase the risk of Alzheimer's disease (AD), translating these findings into effective preventive measures has failed. In addition, the finding that incident ischemic stroke approximately doubles the risk of a patient to develop AD has been recently reinforced. Current knowledge and pathogenetic hypotheses of AD are discussed. The implication of oxidative stress in the development of AD is reviewed, with special emphasis on its sudd...
Source: CNS and Neurological Disorders Drug Targets - Category: Drugs & Pharmacology Authors: Tags: CNS Neurol Disord Drug Targets Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Dickie DA, Quinn TJ, Dawson J Abstract Structural magnetic resonance imaging (MRI) has been used to characterise the appearance of the brain in cerebral small vessel disease (SVD), ischaemic stroke, cognitive impairment, and dementia. SVD is a major cause of stroke and dementia; features of SVD include white matter hyperintensities (WMH) of presumed vascular origin, lacunes of presumed vascular origin, microbleeds, and perivascular spaces. Cognitive impairment and dementia have traditionally been stratified into subtypes of varying origin, e.g., vascular dementia versus dementia of the Alzheimer's type (Al...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
CONCLUSION: Air pollution is associated with increased risk of certain common neurological disorders. More specific studies are needed to investigate the impact of seasonal haze on neurological conditions in Southeast Asia. PMID: 32200394 [PubMed - in process]
Source: Annals of the Academy of Medicine, Singapore - Category: General Medicine Authors: Tags: Ann Acad Med Singapore Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Funding Opportunity RFA-NS-20-012 from the NIH Guide for Grants and Contracts. This initiative will provide two years of support for planning activities necessary for initiating a Phase III clinical trial designed to validate VCID biomarkers and/or treat patients with VCID. The full spectrum of VCID is in scope, and the one or more VCID disorders(s) to be targeted in the trial must be clearly specified in the application, for example (but not limited to): vascular insults including clinical stroke, silent infarcts and microinfarcts, leukoaraiosis, cerebral amyloid angiopathy (CAA), transient ischemic attack (TIA), micro-b...
Source: NIH Funding Opportunities (Notices, PA, RFA) - Category: Research Source Type: funding
Authors: Pluta R, Ułamek-Kozioł M, Januszewski S, Czuczwar S Abstract As the population is aging all over the world, the economic burden of ischemic brain injuries is constantly increasing. Human brain ischemia is one of the leading causes of premature death, significant morbidity and physical and mental disabilities, resulting in a lower quality of life and unusually high costs of health and social care. One of the most difficult problems associated with the pathology of the brain after ischemia is progressive dementia observed in people who survived the stroke. More recently, brain ischemia has been shown to el...
Source: Folia Neuropathologica - Category: Neurology Tags: Folia Neuropathol Source Type: research
In this study, researchers studied 438,952 participants in the UK Biobank, who had a total of 24,980 major coronary events - defined as the first occurrence of non-fatal heart attack, ischaemic stroke, or death due to coronary heart disease. They used an approach called Mendelian randomisation, which uses naturally occurring genetic differences to randomly divide the participants into groups, mimicking the effects of running a clinical trial. People with genes associated with lower blood pressure, lower LDL cholesterol, and a combination of both were put into different groups, and compared against those without thes...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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