Inflammation as a central mechanism in Alzheimer's disease

Alzheimer s & Dementia Translational Research & Clinical Interventions, Journal Year: 2018, Volume and Issue: 4(1), P. 575 - 590

Published: Jan. 1, 2018

Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder that characterized by cognitive decline and the presence of two core pathologies, amyloid β plaques neurofibrillary tangles. Over last decade, sustained immune response in brain has emerged as third pathology AD. The activation brain's resident macrophages (microglia) other cells been demonstrated to exacerbate both tau may serve link pathogenesis disorder. In following review, we provide an overview inflammation AD detailed coverage number microglia‐related signaling mechanisms have implicated Additional information on microglia cytokines are also reviewed. We review potential connection risk factors for how they be related inflammatory mechanisms.

Language: Английский

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The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade

Journal of Alzheimer s Disease, Journal Year: 2018, Volume and Issue: 64(s1), P. S567 - S610

Published: June 12, 2018

The amyloid-␤ oligomer (A␤O) hypothesis was introduced in 1998.It proposed that the brain damage leading to Alzheimer's disease (AD) instigated by soluble, ligand-like A␤Os.This based on discovery fibril-free synthetic preparations of A␤Os were potent CNS neurotoxins rapidly inhibited long-term potentiation and, with time, caused selective nerve cell death (Lambert et al., 1998).The mechanism attributed disrupted signaling involving tyrosine-protein kinase Fyn, mediated an unknown toxin receptor.Over 4,000 articles concerning have been published since then, including more than 400 reviews.A␤Os shown accumulate AD-dependent manner human and animal model tissue experimentally, impair learning memory instigate major facets AD neuropathology, tau pathology, synapse deterioration loss, inflammation, oxidative damage.As reviewed Hayden Teplow 2013, A␤O "has all but supplanted amyloid cascade."Despite emerging understanding role played pathogenesis, not yet received clinical attention given plaques, which at core attempts therapeutics diagnostics are no longer regarded as most pathogenic form A␤.However, if momentum research continues, particularly efforts elucidate key aspects structure, a clear path successful modifying therapy can be envisioned.Ensuring lessons learned from recent, late-stage failures applied appropriately throughout therapeutic development will further enable likelihood near-term.

Language: Английский

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Alzheimer’s disease: experimental models and reality

Acta Neuropathologica, Journal Year: 2016, Volume and Issue: 133(2), P. 155 - 175

Published: Dec. 26, 2016

Language: Английский

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Role of neuroinflammation in neurodegeneration development

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: July 12, 2023

Abstract Studies in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and Amyotrophic lateral sclerosis, Huntington’s so on, have suggested that inflammation is not only a result of neurodegeneration but also crucial player this process. Protein aggregates which are very common pathological phenomenon can induce neuroinflammation further aggravates protein aggregation neurodegeneration. Actually, even happens earlier than aggregation. Neuroinflammation induced by genetic variations CNS cells or peripheral immune may deposition some susceptible population. Numerous signaling pathways range been to be involved the pathogenesis neurodegeneration, although they still far from being completely understood. Due limited success traditional treatment methods, blocking enhancing inflammatory considered promising strategies for therapy many them got exciting results animal models clinical trials. Some them, few, approved FDA usage. Here we comprehensively review factors affecting major pathogenicity sclerosis. We summarize current strategies, both clinic, diseases.

Language: Английский

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Tau and tauopathies

Brain Research Bulletin, Journal Year: 2016, Volume and Issue: 126, P. 238 - 292

Published: Sept. 1, 2016

Language: Английский

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Inflammation and Oxidative Stress: The Molecular Connectivity between Insulin Resistance, Obesity, and Alzheimer’s Disease

Mediators of Inflammation, Journal Year: 2015, Volume and Issue: 2015(1)

Published: Jan. 1, 2015

Type 2 diabetes (T2DM), Alzheimer's disease (AD), and insulin resistance are age-related conditions increased prevalence is of public concern. Recent research has provided evidence that impaired signalling may be a contributory factor to the progression diabetes, dementia, other neurological disorders. (AD) most common subtype dementia. Reduced release (for T2DM) decreased action central development both T2DM AD. A literature search was conducted identify molecular commonalities between obesity, Insulin affects many tissues organs, either through or aberrant changes in glucose lipid (cholesterol triacylglycerol) metabolism concentrations blood. Although epidemiological biological highlighted an incidence cognitive decline AD patients with T2DM, basis cell tissue dysfunction rapidly gaining recognition. As cause consequence, chronic inflammatory response oxidative stress associated amyloid-β (Aβ) protein accumulation, mitochondrial link

Language: Английский

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Therapeutic strategies for Alzheimer's disease in clinical trials

Pharmacological Reports, Journal Year: 2015, Volume and Issue: 68(1), P. 127 - 138

Published: Aug. 6, 2015

Language: Английский

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Plasma tau, neurofilament light chain and amyloid-β levels and risk of dementia; a population-based cohort study

Brain, Journal Year: 2020, Volume and Issue: 143(4), P. 1220 - 1232

Published: Feb. 5, 2020

CSF biomarkers, including total-tau, neurofilament light chain (NfL) and amyloid-β, are increasingly being used to define stage Alzheimer's disease. These biomarkers can be measured more quickly less invasively in plasma may provide important information for early diagnosis of We stored samples clinical data obtained from 4444 non-demented participants the Rotterdam study at baseline (between 2002 2005) during follow-up until January 2016. Plasma concentrations NfL, amyloid-β40 amyloid-β42 were using Simoa NF-light® N3PA assays. Associations between biomarker levels incident all-cause disease dementia assessed Cox proportional-hazard regression models adjusted age, sex, education, cardiovascular risk factors APOE ε4 status. Moreover, rates change over time who developed compared with age sex-matched dementia-free control subjects. During up 14 years follow-up, 549 dementia, 374 cases dementia. A log2 higher level was associated a lower developing or hazard ratio (HR) 0.61 [95% confidence interval (CI), 0.47-0.78; P < 0.0001] 0.59 (95% CI, 0.43-0.79; = 0.0006), respectively. Conversely, NfL [adjusted HR 1.59 1.38-1.83); 1.50 1.26-1.78); 0.0001]. Combining lowest quartile group highest resulted stronger association 9.5 2.3-40.4); 0.002] 15.7 2.1-117.4); 0.0001], NfL. Total-tau not risk. Trajectory analyses revealed that mean increased 3.4 times faster those remained (P 0.0001), values diverged controls 9.6 before diagnosis. Amyloid-β42 began decrease few diagnosis, although decline did reach significance participants. In conclusion, our shows low high each independently combination strongly indicate assess population. levels, specific, also useful monitoring progression

Language: Английский

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The role of type 2 diabetes in neurodegeneration

Neurobiology of Disease, Journal Year: 2015, Volume and Issue: 84, P. 22 - 38

Published: April 26, 2015

Language: Английский

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Oxidative stress in alzheimer’s disease: A review on emergent natural polyphenolic therapeutics

Complementary Therapies in Medicine, Journal Year: 2019, Volume and Issue: 49, P. 102294 - 102294

Published: Dec. 31, 2019

Language: Английский

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