scholarly journals Innate Immune System and Inflammation in Alzheimer's Disease: From Pathogenesis to Treatment

2014 ◽  
Vol 21 (2-3) ◽  
pp. 79-87 ◽  
Author(s):  
Maria Serpente ◽  
Rossana Bonsi ◽  
Elio Scarpini ◽  
Daniela Galimberti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Innate Immune System ◽  
Innate Immune

scholarly journals The Innate Immune System in Alzheimer’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Allal Boutajangout ◽  
Thomas Wisniewski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Innate Immune System ◽  
Late Onset ◽  
Innate Immune ◽  
Amyloid Angiopathy ◽  
Functional Variant ◽  
The Central Nervous System ◽  
Congophilic Amyloid Angiopathy

Alzheimer’s disease (AD) is the leading cause for dementia in the world. It is characterized by two biochemically distinct types of protein aggregates: amyloidβ(Aβ) peptide in the forms of parenchymal amyloid plaques and congophilic amyloid angiopathy (CAA) and aggregated tau protein in the form of intraneuronal neurofibrillary tangles (NFT). Several risk factors have been discovered that are associated with AD. The most well-known genetic risk factor for late-onset AD is apolipoprotein E4 (ApoE4) (Potter and Wisniewski (2012), and Verghese et al. (2011)). Recently, it has been reported by two groups independently that a rare functional variant (R47H) of TREM2 is associated with the late-onset risk of AD. TREM2 is expressed on myeloid cells including microglia, macrophages, and dendritic cells, as well as osteoclasts. Microglia are a major part of the innate immune system in the CNS and are also involved in stimulating adaptive immunity. Microglia express several Toll-like receptors (TLRs) and are the resident macrophages of the central nervous system (CNS). In this review, we will focus on the recent advances regarding the role of TREM2, as well as the effects of TLRs 4 and 9 on AD.

Perturbation of the transcriptome: implications of the innate immune system in Alzheimer's disease

2016 ◽  
Vol 26 ◽  
pp. 47-53 ◽  
Author(s):  
Fuhai Song ◽  
Ying Qian ◽  
Xing Peng ◽  
Guangchun Han ◽  
Jiajia Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Innate Immune System ◽  
Innate Immune

Role of the peripheral innate immune system in the development of Alzheimer's disease

2018 ◽  
Vol 107 ◽  
pp. 59-66 ◽  
Author(s):  
Aurélie Le Page ◽  
Gilles Dupuis ◽  
Eric H. Frost ◽  
Anis Larbi ◽  
Graham Pawelec ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Innate Immune System ◽  
Innate Immune

scholarly journals Genetic variability associated with OAS1 expression in myeloid cells increases the risk of Alzheimer's disease and severe COVID-19 outcomes

2021 ◽  
Author(s):  
Naciye Magusali ◽  
Andrew C Graham ◽  
Thomas M Piers ◽  
Pantila Panichnantakul ◽  
Umran Yaman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Critical Illness ◽  
Inflammatory Response ◽  
Innate Immune System ◽  
Transcriptional Network ◽  
Innate Immune ◽  
Genome Wide Association Studies ◽  
Oligoadenylate Synthetase

Genome-wide association studies of late-onset Alzheimer's disease (AD) have highlighted the importance of variants associated with genes expressed by the innate immune system in determining risk for AD. Recently, we and others have shown that genes associated with variants that confer risk for AD are significantly enriched in transcriptional networks expressed by amyloid-responsive microglia. This allowed us to predict new risk genes for AD, including the interferon-responsive oligoadenylate synthetase 1 (OAS1). However, the function of OAS1 within microglia and its genetic pathway are not known. Using genotyping from 1,313 individuals with sporadic AD and 1,234 control individuals, we confirm that the OAS1 variant, rs1131454, is associated with increased risk for AD and decreased OAS1 expression. Moreover, we note that the same locus was recently associated with critical illness in response to COVID-19, linking variants that are associated with AD and a severe response to COVID-19. By analysing single-cell RNA-sequencing (scRNA-seq) data of isolated microglia from APPNL-G-F knock-in and wild-type C57BL/6J mice, we identify a transcriptional network that is significantly upregulated with age and amyloid deposition, and contains the mouse orthologue Oas1a, providing evidence that Oas1a plays an age-dependent function in the innate immune system. We identify a similar interferon-related transcriptional network containing OAS1 by analysing scRNA-seq data from human microglia isolated from individuals with AD. Finally, using human iPSC-derived microglial cells (h-iPSC-Mg), we see that OAS1 is required to limit the pro-inflammatory response of microglia. When stimulated with interferon-gamma (IFN-γ), we note that cells with lower OAS1 expression show an exaggerated pro-inflammatory response, with increased expression and secretion of TNF-α. Collectively, our data support a link between genetic risk for AD and susceptibility to critical illness with COVID-19 centred on OAS1 and interferon signalling, a finding with potential implications for future treatments of both AD and COVID-19, and the development of biomarkers to track disease progression.

scholarly journals The Viral Hypothesis in Alzheimer’s Disease: Novel Insights and Pathogen-Based Biomarkers

2020 ◽  
Vol 10 (3) ◽  
pp. 74 ◽  
Author(s):  
Sean X Naughton ◽  
Urdhva Raval ◽  
Giulio M. Pasinetti
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Innate Immune System ◽  
Antimicrobial Properties ◽  
Significant Risk ◽  
Amyloid Β ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Viral Hypothesis

Early diagnosis of Alzheimer’s disease (AD) and the identification of significant risk factors are necessary to better understand disease progression, and to develop intervention-based therapies prior to significant neurodegeneration. There is thus a critical need to establish biomarkers which can predict the risk of developing AD before the onset of cognitive decline. A number of studies have indicated that exposure to various microbial pathogens can accelerate AD pathology. Additionally, several studies have indicated that amyloid-β possess antimicrobial properties and may act in response to infection as a part of the innate immune system. These findings have led some to speculate that certain types of infections may play a significant role in AD pathogenesis. In this review, we will provide an overview of studies which suggest pathogen involvement in AD. Additionally, we will discuss a number of pathogen-associated biomarkers which may be effective in establishing AD risk. Infections that increase the risk of AD represent a modifiable risk factor which can be treated with therapeutic intervention. Pathogen-based biomarkers may thus be a valuable tool for evaluating and decreasing AD risk across the population.

Systemic inflammation and Alzheimer's disease

2011 ◽  
Vol 39 (4) ◽  
pp. 898-901 ◽  
Author(s):  
Clive Holmes ◽  
Joe Butchart
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Systemic Inflammation ◽  
Innate Immune System ◽  
Innate Immune ◽  
Sickness Behaviour ◽  
Show Evidence ◽  
Ad Alzheimer’S Disease ◽  
Communication Pathway ◽  
Novel Therapeutic

A number of studies demonstrate disturbances of the central innate immune system in AD (Alzheimer's disease). In animal and human studies, there is evidence of close communication between systemic and central innate immune systems. Animal models of neurodegeneration show evidence of an exaggerated central innate immune response following systemic inflammation. Clinical studies of AD show evidence of increased cognitive decline and exaggerated sickness behaviour in response to systemic inflammation. Recognition of this communication pathway offers alternative explanations for a number of recognized risk factors in the development and progression of AD and highlights the potential of the manipulation of systemic innate immunity as a novel therapeutic approach.

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