The Impact of Ageing on the CNS Immune Response in Alzheimer’s Disease

Chee, Stephan En Jie; Solito, Egle

doi:10.3389/fimmu.2021.738511

Cited by 18 publications

(15 citation statements)

References 161 publications

(244 reference statements)

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“…According to the immune hypothesis proposed by Fiala and colleagues [ 185 , 186 ], a dysfunctional immune system may be the main player in the pathogenesis of AD [ 187 ]. In this view, a number of dysfunctional immune elements have been implicated.…”

Section: Resultsmentioning

confidence: 99%

Therapeutic roles of plants for 15 hypothesised causal bases of Alzheimer’s disease

Tyler

2022

Nat. Prod. Bioprospect.

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Alzheimer’s disease (AD) is progressive and ultimately fatal, with current drugs failing to reverse and cure it. This study aimed to find plant species which may provide therapeutic bioactivities targeted to causal agents proposed to be driving AD. A novel toolkit methodology was employed, whereby clinical symptoms were translated into categories recognized in ethnomedicine. These categories were applied to find plant species with therapeutic effects, mined from ethnomedical surveys. Survey locations were mapped to assess how this data is at risk. Bioactivities were found of therapeutic relevance to 15 hypothesised causal bases for AD. 107 species with an ethnological report of memory improvement demonstrated therapeutic activity for all these 15 causal bases. The majority of the surveys were found to reside within biodiversity hotspots (centres of high biodiversity under threat), with loss of traditional knowledge the most common threat. Our findings suggest that the documented plants provide a large resource of AD therapeutic potential. In demonstrating bioactivities targeted to these causal bases, such plants may have the capacity to reduce or reverse AD, with promise as drug leads to target multiple AD hallmarks. However, there is a need to preserve ethnomedical knowledge, and the habitats on which this knowledge depends. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

Therapeutic roles of plants for 15 hypothesised causal bases of Alzheimer’s disease

Tyler

2022

Nat. Prod. Bioprospect.

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“…The United States had the largest record counts among the top 100 cited articles, which owns the overwhelming number of citations and record counts, indicating that the United States was the most productive and influential country in this field. With the aging of the global population, the burden of NDs is increasing yearly ( Chee and Solito, 2021 ). In the United States, Alzheimer’s disease affected five million people and caused a huge amount of healthcare costs ( Hurd et al, 2013 ), it has been predicted that the number of dementia in the United States will increase by 35% by 2030 ( Petersen et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

The Top-Cited Original Articles on the Role of Microglia in Neurodegenerative Diseases: A Bibliometric and Visualized Study

Sun

et al. 2022

Front. Aging Neurosci.

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BackgroundMicroglia participants to neuronal loss during brain development, inflammation, ischemia, and neurodegeneration. This bibliometric and visualized study aimed to confirm the top 100 cited original research in the field and to analyze their characteristics.MethodsThe Web of Science database (WOS) was retrieved using the specific search strategy. The top 100 cited original articles that focused on the role of microglia in neurodegenerative diseases (NDs) were filtered by two researchers independently. The trend of yearly publications and citations, citation densities, languages, and global contributions were analyzed. The highly cited countries, authors, institutions, and journals were visualized by bibliographic coupling analysis. The highly cited authors and journals in the references were visualized by co-citation analysis. The research hotspots were revealed by co-occurrence analysis and burst detection of author keywords.ResultsThe top 100 cited articles were published during the period 1988 to 2019. The peak of publication occurred in 2005 and 2006. The yearly total citations presented a rising trend. The highly cited articles were contributed by 26 countries, the United States was the country with the overwhelming number of publications and cited times. Stevens, Beth was the author with the largest number of cited times. Mcgeer PL was the author most frequently cited in the references. Harvard University was the institution with the greatest number of cited times and publications. Nature was the journal with the largest number of cited times. Journal of neuroscience was both the most often published and most frequently cited journal in the references. “Microglia”, “inflammation”, “Alzheimer’s disease” were the most frequently used keywords, and their average occurred time was around 2005. “Dementia,” “delirium,” “priming” were keywords that averagely occurred around 2010. The burst detection revealed that “TNF-beta,” “macrophage,” and “inflammation” were keywords that frequently burst in recent years.ConclusionThis bibliometric and visualized study revealed the top 100 cited original research that discussed the role of microglia in NDs. The United States was the biggest contributor, Harford University was the most influential institution. Journal of Neuroscience was the most often published and cited journal. Alzheimer’s disease was the hotspot in microglia and NDs. Recent research mainly focused on inflammation.

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“…Because LOAD requires a significant percentage of one's lifespan to have passed 1,3 , it is considered here to represent a disease involving senescence. This view is reinforced by evidence of shortened telomere lengths and increased immunosenescence in LOAD patients 29,30,66,67 . Tissue dysfunction and cognitive impairment in multiple mouse models have also been tied to senescent cell burden in the brain, where removing senescent cells has been shown to lower inflammation and increase the performance in spatial memory tasks 27,68,69 .…”

Section: Cns Glia Lose Homeostatic Capacity With Agingmentioning

confidence: 91%

The Glial Aging & Senescence Hypothesis of Late-onset Alzheimer’s

Lau¹,

Ramer²,

Tremblay³

2022

Preprint

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Alzheimer’s disease (AD) predominantly occurs as a late-onset form (LOAD), involving neurodegeneration and cognitive decline with progressive memory loss. Over time, risk factors and aging promote accumulation of well-known AD pathologies in oxidative stress, amyloid-beta and tau protein pathology, as well as inflammation. Homeostatic glial functions regulate and suppress these AD pathologies; however, other glial states involve increased pro-inflammatory cytokine release and further pathology accumulation. Different stresses can additionally induce cellular senescence, or an irreversible differentiation process resulting in decreased supportive functions and increased, pro-inflammatory cytokine release. While these pathophysiological underpinnings all contribute to LOAD, they require temporal and mechanistic integration. This perspective hypothesizes that when individuals have threshold senescent glia accumulation, they transition from healthy cognition into mild cognitive impairment and LOAD diagnosis. Particularly, senescent microglia are predicted to represent a final threshold required for the tau pathology burden and spreading that corresponds to sustained neurodegeneration and dementia severity. We first explore age-related decline in glia that promote increases in AD pathologies, and then discuss emerging evidence linking oxidative stress, neurons containing tau pathology, and amyloid-beta to microglia, oligodendrocyte progenitor cell, and astrocyte senescence. Our hypothesis proposes that senescent astrocytes and oligodendrocyte progenitors pressure microglia to phagocytose neurons containing tau pathology. The resulting senescent microglia would form neuritic plaques and induce paracrine senescence transitioning into a progressive clinical dementia presentation. This predictive hypothesis can potentially account for why medications used to treat LOAD fail, as previous treatments have not reduced senescent glial burden. It is also coherent with the predominant hypotheses surrounding LOAD, generates testable hypotheses about LOAD, and increases rationale in testing senolytics as targeted treatments for LOAD arrest and reversal.

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The Impact of Ageing on the CNS Immune Response in Alzheimer’s Disease

Cited by 18 publications

References 161 publications

Therapeutic roles of plants for 15 hypothesised causal bases of Alzheimer’s disease

Therapeutic roles of plants for 15 hypothesised causal bases of Alzheimer’s disease

The Top-Cited Original Articles on the Role of Microglia in Neurodegenerative Diseases: A Bibliometric and Visualized Study

The Glial Aging & Senescence Hypothesis of Late-onset Alzheimer’s

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