Microglial priming in Alzheimer’s disease

Li, Junwei; Zong, Yu; Cao, Xi‐Peng; Tan, Lin; Tan, Lan

doi:10.21037/atm.2018.04.22

Cited by 81 publications

(85 citation statements)

References 129 publications

(153 reference statements)

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“…As PD can prime macrophages either through microbial factors (e.g., lipopolysaccharide) 54 , 55 or by activation of other immune and non-immune cells 56 , 57 , microglia priming, activation, and polarization due to PD may be plausible 24 . The exaggerated response of primed microglia is known to contribute to the pathogenesis of AD 58 . In contrast to our previous study where we reported a significant increase in the level of some inflammatory cytokines (GM-CSF, IL-6, IFN-γ, and IL-1β) in 3-month-old 5xFAD mice 3 , in the current study using 8-month-old 5xFAD mice, these specific cytokines were not increased.…”

Section: Discussionmentioning

confidence: 99%

Microglial response to experimental periodontitis in a murine model of Alzheimer’s disease

Kantarcı¹,

Tognoni

Yaghmoor³

et al. 2020

Sci Rep

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Periodontal disease (PD) has been suggested to be a risk factor for Alzheimer’s disease (AD). We tested the impact of ligature-induced PD on 5xFAD mice and WT littermates. At baseline, 5xFAD mice presented significant alveolar bone loss compared to WT mice. After the induction of PD, both WT and 5xFAD mice experienced alveolar bone loss. PD increased the level of Iba1-immunostained microglia in WT mice. In 5xFAD mice, PD increased the level of insoluble Aβ42. The increased level in Iba1 immunostaining that parallels the accumulation of Aβ in 5xFAD mice was not affected by PD except for a decrease in the dentate gyrus. Analysis of double-label fluorescent images showed a decline in Iba1 in the proximity of Aβ plaques in 5xFAD mice with PD compared to those without PD suggesting a PD-induced decrease in plaque-associated microglia (PAM). PD reduced IL-6, MCP-1, GM-CSF, and IFN-γ in brains of WT mice and reduced IL-10 in 5xFAD mice. The data demonstrated that PD increases neuroinflammation in WT mice and disrupts the neuroinflammatory response in 5xFAD mice and suggest that microglia is central to the association between PD and AD.

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Section: Discussionmentioning

confidence: 99%

Microglial response to experimental periodontitis in a murine model of Alzheimer’s disease

Kantarcı¹,

Tognoni

Yaghmoor³

et al. 2020

Sci Rep

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“…Microglia and astrocytes primed by HIV may play important roles in engulfing and purging Aβ plaques from the brain. 46 In severe HAD with a disrupted blood-brain barrier, amyloid clearance may be enhanced in some individuals. Also, in treated PLHIV, amyloid clearance may occur through HIV-1 Tat priming and activation of microglia.…”

Section: Discussionmentioning

confidence: 99%

Brain amyloid in virally suppressed HIV-associated neurocognitive disorder

Howdle

Quidé

Kassem

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo determine whether virally suppressed HIV neuropathogenesis, a chronic neuroinflammatory state, promotes abnormal brain amyloid deposition.MethodsA total of 10 men with virally suppressed HIV-associated neurocognitive disorder (HAND), aged 46–68 years, underwent 11C-labeled Pittsburgh compound B PET. Data from the Australian Imaging, Biomarkers and Lifestyle (AIBL), including 39 cognitively normal individuals (aged 60–74 years), 7 individuals with mild cognitive impairment (MCI) (aged 64–71 years), and 11 individuals with Alzheimer disease (AD) (aged 55–74 years), were used as reference. Apart from more women, the AIBL cohort was demographically comparable with the HIV sample. Also, the AIBL PET data did not differ by sex. Cerebellum standardized uptake value ratio amyloid values within 22 regions of interest were estimated. In the HIV sample, apolipoprotein E (APOE) was available in 80%, CSF biomarkers in 60%, and 8–10 years of long-term health outcomes in 100%.ResultsHAND and the AIBL group with no cognitive deficits had similar amyloid deposition, which was lower than that in both the MCI and AD groups. At the individual level, one HAND case showed high amyloid deposition consistent with AD. This case also had a CSF-AD–like profile and an E4/E4 for APOE. Clinically, this case declined over 18 years with mild HAND symptoms first, followed by progressive memory decline 8–9 years after the study PET, then progression to severe dementia within 2–3 years, and lived a further 6 years. Another HAND case showed increased amyloid deposition restricted to the hippocampi. Two other HAND cases showed abnormally decreased amyloid in subcortical areas.ConclusionsRelative to cognitively normal older controls, brain amyloid burden does not differ in virally suppressed HAND at the group level. However, individual analyses show that abnormally high and low amyloid burden occur.

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“…Neuroinflammation plays a key role in the etio-pathogenesis of Alzheimer's disease and other neurodegenerative disorders (Edison et al, 2008;Fernandez-Botran et al, 2011;Fan et al, 2015b;Stefaniak and O'Brien, 2016). Pre-clinical models (Heppner et al, 2015;Hoeijmakers et al, 2016;Villegas-Llerena et al, 2016;Li et al, 2018;Wang et al, 2018), and research in humans (Fernandez-Botran et al, 2011;Edison et al, 2013;Fan et al, 2015b;Stefaniak and O'Brien, 2016), demonstrate that microglia of the brain's innate immune system are activated in Alzheimer's and related diseases. In addition, genetic association studies have demonstrated a link between Alzheimer's disease and polymorphisms and mutations of genes linked to immune responses (Villegas-Llerena et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Although the mechanisms and mediators of inflammatory risk in Alzheimer's disease are not fully understood, synaptic and neuronal injury may arise from the release of cytokines and pro-inflammatory molecules such as interleukin-1ß and TGF-ß (Fernandez-Botran et al, 2011), or direct microglial injury to synapses . These, in turn, impair synaptic function, network communication, and may accelerate neurodegeneration and synaptic loss (Heppner et al, 2015;Hoeijmakers et al, 2016;Villegas-Llerena et al, 2016;Li et al, 2018;Wang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Neuroinflammation and functional connectivity in Alzheimer’s disease: interactive influences on cognitive performance

Passamonti

Tsvetanov

Jones

et al. 2019

Preprint

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Neuroinflammation is a key part of the etio-pathogenesis of Alzheimer's disease. We test the relationship between neuroinflammation and the disruption of functional connectivity in large-scale networks, and their joint influence on cognitive impairment.We combined [ 11 C]PK11195 positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI) in 28 humans (13 females/15 males) with clinical diagnosis of probable Alzheimer's disease or mild cognitive impairment with positive PET biomarker for amyloid, and 14 age-, sex-, and education-matched healthy humans (8 Significance StatementNeuroinflammation is an important aspect of Alzheimer's disease (AD), but it was not known whether the influence of neuroinflammation on brain network function in humans was important for cognitive deficit.Our study provides clear evidence that in vivo neuroinflammation in AD impairs largescale network connectivity; and that the link between inflammation and functional network connectivity is relevant to cognitive impairment.We suggest that future studies should address how neuroinflammation relates to network function as AD progresses; and whether the neuroinflammation in AD is reversible, as the basis of immunotherapeutic strategies to slow the progression of AD.

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Microglial priming in Alzheimer’s disease

Cited by 81 publications

References 129 publications

Microglial response to experimental periodontitis in a murine model of Alzheimer’s disease

Microglial response to experimental periodontitis in a murine model of Alzheimer’s disease

Brain amyloid in virally suppressed HIV-associated neurocognitive disorder

Neuroinflammation and functional connectivity in Alzheimer’s disease: interactive influences on cognitive performance

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