A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease

Cell, Год журнала: 2017, Номер 169(7), С. 1276 - 1290.e17

Опубликована: Июнь 1, 2017

Язык: Английский

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Inflammation as a central mechanism in Alzheimer's disease

Alzheimer s & Dementia Translational Research & Clinical Interventions, Год журнала: 2018, Номер 4(1), С. 575 - 590

Опубликована: Янв. 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.

Язык: Английский

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The Cellular Phase of Alzheimer’s Disease

Cell, Год журнала: 2016, Номер 164(4), С. 603 - 615

Опубликована: Фев. 1, 2016

Язык: Английский

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Microglia in Alzheimer’s disease

Journal of Clinical Investigation, Год журнала: 2017, Номер 127(9), С. 3240 - 3249

Опубликована: Авг. 31, 2017

Microglia are brain-resident myeloid cells that mediate key functions to support the CNS. express a wide range of receptors act as molecular sensors, which recognize exogenous or endogenous CNS insults and initiate an immune response. In addition their classical cell function, microglia guardians brain by promoting phagocytic clearance providing trophic ensure tissue repair maintain cerebral homeostasis. Conditions associated with loss homeostasis changes induce several dynamic microglial processes, including cellular morphology, surface phenotype, secretory mediators, proliferative responses (referred "activated state"). Activated represent common pathological feature neurodegenerative diseases, Alzheimer's disease (AD). Cumulative evidence suggests inflammatory activity in AD is increased while microglial-mediated mechanisms compromised. perpetually engaged mutual interaction surrounding environment CNS; thus, diverse reactions at different stages may open new avenues for therapeutic intervention modification activities. this Review, role pathogenesis modulation modality will be discussed.

Язык: Английский

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Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift

Neuron, Год журнала: 2017, Номер 95(6), С. 1246 - 1265

Опубликована: Сен. 1, 2017

Язык: Английский

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Eliminating microglia in Alzheimer’s mice prevents neuronal loss without modulating amyloid-β pathology

Brain, Год журнала: 2016, Номер 139(4), С. 1265 - 1281

Опубликована: Фев. 26, 2016

In addition to amyloid-β plaque and tau neurofibrillary tangle deposition, neuroinflammation is considered a key feature of Alzheimer's disease pathology. Inflammation in characterized by the presence reactive astrocytes activated microglia surrounding amyloid plaques, implicating their role pathogenesis. Microglia healthy adult mouse depend on colony-stimulating factor 1 receptor (CSF1R) signalling for survival, pharmacological inhibition this results rapid elimination nearly all central nervous system. study, we set out determine if chronically brain are also dependent CSF1R signalling, so, how these cells contribute Ten-month-old 5xfAD mice were treated with selective inhibitor month, resulting ∼80% microglia. Chronic microglial does not alter levels or load; however, it rescue dendritic spine loss prevent neuronal mice, as well reduce overall neuroinflammation. Importantly, behavioural testing revealed improvements contextual memory. Collectively, demonstrate that loss, memory impairments but do mediate protect from Microglia-mediated inflammation driving force Spangenberg et al . show improves cognitive function ameliorates synaptic/neuronal without altering load. Thus, act downstream plaques damage brain.

Язык: Английский

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Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease

Journal of Neuroinflammation, Год журнала: 2017, Номер 14(1)

Опубликована: Янв. 3, 2017

Treatment of mild-moderate Alzheimer's disease (AD) subjects (N = 119) for 52 weeks with the SIRT1 activator resveratrol (up to 1 g by mouth twice daily) attenuates progressive declines in CSF Aβ40 levels and activities daily living (ADL) scores. For this retrospective study, we examined banked plasma samples from a subset AD Aβ42 <600 ng/ml (biomarker-confirmed AD) at baseline 19 resveratrol-treated N placebo-treated). We utilized multiplex Xmap technology measure markers neurodegenerative metalloproteinases (MMPs) parallel samples. Compared placebo-treated group, weeks, markedly reduced MMP9 increased macrophage-derived chemokine (MDC), interleukin (IL)-4, fibroblast growth factor (FGF)-2. baseline, MMP10 decreased IL-12P40, IL12P70, RANTES. In analysis, treatment attenuated mini-mental status examination (MMSE) scores, change ADL (ADCS-ADL) during 52-week trial, but did not alter tau levels. Collectively, these data suggest that decreases MMP9, modulates neuro-inflammation, induces adaptive immunity. activation may be viable target or prevention disorders. ClinicalTrials.gov NCT01504854

Язык: Английский

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A Breakdown in Metabolic Reprogramming Causes Microglia Dysfunction in Alzheimer's Disease

Cell Metabolism, Год журнала: 2019, Номер 30(3), С. 493 - 507.e6

Опубликована: Июнь 27, 2019

Язык: Английский

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Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer’s disease

Scientific Reports, Год журнала: 2016, Номер 6(1)

Опубликована: Июль 21, 2016

Abstract Severe amyloidosis and plaque-localized neuro-inflammation are key pathological features of Alzheimer’s disease (AD). In addition to astrocyte microglial reactivity, emerging evidence suggests a role gut microbiota in regulating innate immunity influencing brain function. Here, we examine the host microbiome APP SWE /PS1 ΔE9 mouse model AD. We show that prolonged shifts microbial composition diversity induced by long-term broad-spectrum combinatorial antibiotic treatment regime decreases Aβ plaque deposition. also levels soluble elevated circulating cytokine chemokine signatures altered this setting. Finally, observe attenuated plaque-localised glial reactivity these mice significantly morphology. These findings suggest community can regulate mechanisms impact amyloidosis.

Язык: Английский

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Protein misfolding in neurodegenerative diseases: implications and strategies

Translational Neurodegeneration, Год журнала: 2017, Номер 6(1)

Опубликована: Март 13, 2017

A hallmark of neurodegenerative proteinopathies is the formation misfolded protein aggregates that cause cellular toxicity and contribute to proteostatic collapse. Therapeutic options are currently being explored target different steps in production processing proteins implicated disease, including synthesis, chaperone-assisted folding trafficking, degradation via proteasome autophagy pathways. Other therapies, like mTOR inhibitors activators heat shock response, can rebalance entire network. However, there major challenges impact development novel incomplete knowledge druggable disease targets their mechanism action as well a lack biomarkers monitor progression therapeutic response. notable creation collaborative ecosystems include patients, clinicians, basic translational researchers, foundations regulatory agencies promote scientific rigor clinical data accelerate therapies prevent, reverse or delay proteinopathies.

Язык: Английский

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