Alzheimer’s disease and gut microbiota

Science China Life Sciences, Journal Year: 2016, Volume and Issue: 59(10), P. 1006 - 1023

Published: Aug. 26, 2016

Alzheimer's disease (AD) is a most common neurodegenerative disorder, which associates with impaired cognition. Gut microbiota can modulate host brain function and behavior via microbiota-gut-brain axis, including cognitive behavior. Germ-free animals, antibiotics, probiotics intervention diet induce alterations of gut physiology also behavior, increasing or decreasing risks AD. The increased permeability intestine blood-brain barrier induced by disturbance will increase the incidence neurodegeneration disorders. microbial metabolites their effects on neurochemical changes may decrease risk Pathogenic microbes infection AD, meanwhile, onset AD support "hygiene hypothesis". All results suggest that begin in gut, closely related to imbalance microbiota. Modulation through personalized beneficial probably become new treatment for

Language: Английский

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Neuroinflammation: Microglia and T Cells Get Ready to Tango

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 8

Published: Jan. 24, 2018

In recent years, many paradigms concerning central nervous system (CNS) immunology have been challenged and shifted, including the discovery of CNS-draining lymphatic vessels, origin functional diversity microglia, impact T cells on CNS immunological homeostasis role neuroinflammation in neurodegenerative diseases. parallel, antigen presentation outside has revealed vital antigen-presenting maintaining tolerance toward self-proteins, thwarting auto-immunity. Here, we review findings that unite these shifted microglial functioning, presentation, CNS-directed cell activation, focusing common It provides an important update adaptive immunity, novel targets, a concept microglia T-cell equilibrium.

Language: Английский

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16S rRNA Next Generation Sequencing Analysis Shows Bacteria in Alzheimer’s Post-Mortem Brain

Frontiers in Aging Neuroscience, Journal Year: 2017, Volume and Issue: 9

Published: June 20, 2017

The neurological deterioration associated with Alzheimer’s disease, involving accumulation of amyloid-beta peptides and neurofibrillary tangles, is evident neuroinflammation. This now seen to be a significant contributor pathology. Recently the tenet privileged status brain, regarding microbial compromise, has been questioned, particularly in terms neurodegenerative diseases. It being considered that microbiological incursion into central nervous system could either an initiator or these. novel study using 16S ribosomal gene-specific Next Generation Sequencing extracted brain tissue. A comparison was made bacterial species content both frozen formaldehyde fixed sections small cohort Alzheimer-affected cases those cognitively unimpaired (normal). Our findings suggest increase populations Alzheimer tissue compared normal.

Language: Английский

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The Physiological Roles of Amyloid-β Peptide Hint at New Ways to Treat Alzheimer's Disease

Frontiers in Aging Neuroscience, Journal Year: 2018, Volume and Issue: 10

Published: April 25, 2018

Amyloid-ß (Aß) is best known as the misfolded peptide that involved in pathogenesis of Alzheimer's disease (AD), and it currently primary therapeutic target attempts to arrest course this disease. This notoriety has overshadowed evidence Aß serves several important physiological functions. present throughout lifespan, been found all vertebrates examined thus far, its molecular sequence shows a high degree conservation. These features are typical factor contributes significantly biological fitness, suggestion supported by functions beneficial for brain. The putative roles include protecting body from infections, repairing leaks blood-brain barrier, promoting recovery injury, regulating synaptic function. Evidence these comes vitro vivo studies, which have shown cellular production rapidly increases response challenge often diminishes upon recovery. further adverse outcomes clinical trials attempted deplete order treat AD. We suggest anti-Aß therapies will produce fewer effects if triggers deposition (e.g. pathogens, hypertension diabetes) addressed first.

Language: Английский

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CNS infection and immune privilege

Nature reviews. Neuroscience, Journal Year: 2018, Volume and Issue: 19(11), P. 655 - 671

Published: Oct. 11, 2018

Language: Английский

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Role of neuroinflammation in neurodegeneration: new insights

Alzheimer s Research & Therapy, Journal Year: 2017, Volume and Issue: 9(1)

Published: March 3, 2017

Previously, the contribution of peripheral infection to cognitive decline was largely overlooked however, past 15 years have established a key role for infectious pathogens in progression age-related neurodegeneration. It is now accepted that immune privilege brain not absolute, and cells central nervous system are sensitive both inflammatory events occurring periphery infiltration cells. This particularly relevant Alzheimer's disease, which it has been demonstrated patients more vulnerable infection-related changes. can occur from typical challenges such as respiratory tract infections, although number specific viral, bacterial, fungal also associated with development disease. To date, clear whether these microorganisms directly related disease or if they opportune easily colonize those dementia exacerbate ongoing inflammation observed individuals. review will discuss impact each challenges, examine changes known age system, may contribute vulnerability infection-induced decline.

Language: Английский

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Targeting Neuroinflammation to Treat Alzheimer’s Disease

CNS Drugs, Journal Year: 2017, Volume and Issue: 31(12), P. 1057 - 1082

Published: Dec. 1, 2017

Over the past few decades, research on Alzheimer's disease (AD) has focused pathomechanisms linked to two of major pathological hallmarks extracellular deposition beta-amyloid peptides and intra-neuronal formation neurofibrils. Recently, a third component, neuroinflammatory reaction mediated by cerebral innate immune cells, entered spotlight, prompted findings from genetic, pre-clinical, clinical studies. Various proteins that arise during neurodegeneration, including beta-amyloid, tau, heat shock proteins, chromogranin, among others, act as danger-associated molecular patterns, that—upon engagement pattern recognition receptors—induce inflammatory signaling pathways ultimately lead production release mediators. These may have beneficial effects but compromise neuronal function cause cell death. The current review, assembled participants Chiclana Summer School Neuroinflammation 2016, provides an overview our understanding AD-related processes. We describe principal cellular players in inflammation they pertain AD, examine modifying factors, discuss potential future therapeutic targets.

Language: Английский

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Cathepsin B plays a critical role in inducing Alzheimer’s disease-like phenotypes following chronic systemic exposure to lipopolysaccharide from Porphyromonas gingivalis in mice

Brain Behavior and Immunity, Journal Year: 2017, Volume and Issue: 65, P. 350 - 361

Published: June 11, 2017

A number of clinical and experimental studies have revealed a strong association between periodontitis accelerated cognitive decline in Alzheimer’s disease (AD); however, the mechanism is unknown. In present study, we tested hypothesis that cathepsin (Cat) B plays critical role initiation neuroinflammation neural dysfunction following chronic systemic exposure to lipopolysaccharide from Porphyromonas gingivalis (PgLPS) mice (1 mg/kg, daily, intraperitoneally). Young (2 months old) middle-aged (12 wild-type (WT; C57BL/6N) or CatB-deficient (CatB−/−) were exposed PgLPS daily for 5 consecutive weeks. The learning memory function assessed using passive avoidance test, expression amyloid precursor protein (APP), CatB, TLR2 IL-1β was analyzed brain tissues by immunohistochemistry Western blotting. We found five weeks induced deficits with intracellular accumulation Aβ neurons WT mice, but not young CatB−/− mice. significantly increased CatB both microglia while mature restricted hippocampus ones. vitro studies, µg/ml) stimulation upregulated mean mRNA IL-1β, downregulated levels IκBα cultured MG6 as well primary which inhibited CatB-specific inhibitor CA-074Me Furthermore, APP hippocampal after treatment conditioned medium PgLPS-treated microglia, neutralized anti-IL-1beta, directly. Taken together, these findings indicate induces AD-like phenotypes, including microglia-mediated neuroinflammation, impairment functions CatB-dependent manner. propose may be therapeutic target preventing periodontitis-associated AD.

Language: Английский

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The Microbiome in Psychology and Cognitive Neuroscience

Trends in Cognitive Sciences, Journal Year: 2018, Volume and Issue: 22(7), P. 611 - 636

Published: June 12, 2018

Language: Английский

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Alzheimer’s Amyloid-β is an Antimicrobial Peptide: A Review of the Evidence

Journal of Alzheimer s Disease, Journal Year: 2018, Volume and Issue: 62(4), P. 1495 - 1506

Published: Feb. 28, 2018

The amyloid-β (Aβ) peptide has long been considered to be the driving force behind Alzheimer’s disease (AD). However, clinical trials that have successfully reduced Aβ burden in brain not slowed cognitive decline, and some instances, resulted adverse outcomes. While these results can interpreted different ways, a more nuanced picture of is emerging takes into account facts evolutionarily conserved present throughout life cognitively normal individuals. Recent evidence indicates role for as an antimicrobial (AMP), class innate immune defense molecule utilizes fibrillation protect host from wide range infectious agents. In humans animal models, infection frequently leads increased amyloidogenic processing protein precursor (AβPP) resultant fibrillary aggregates Aβ. Evidence vitro vivo studies demonstrates oligomers potent, broad-spectrum properties by forming fibrils entrap pathogens disrupt cell membranes. Importantly, overexpression confers resistance both bacteria viruses. may explain why rates observed AD depleted Perhaps progress toward cure will accelerate once treatment strategies begin take likely physiological functions this enigmatic peptide.

Language: Английский

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