Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Language: Английский

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Cell type-specific roles of APOE4 in Alzheimer disease

Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: 25(2), P. 91 - 110

Published: Jan. 8, 2024

Language: Английский

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The use of neuroimaging techniques in the early and differential diagnosis of dementia

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(10), P. 4084 - 4097

Published: Aug. 22, 2023

Dementia is a leading cause of disability and death worldwide. At present there no disease modifying treatment for any the most common types dementia such as Alzheimer's (AD), Vascular dementia, Lewy Body (LBD) Frontotemporal (FTD). Early accurate diagnosis subtype critical to improving clinical care developing better treatments. Structural molecular imaging has contributed understanding pathophysiology neurodegenerative dementias increasingly being adopted into practice early diagnosis. In this review we summarise contribution made with particular focus on multimodal magnetic resonance (MRI) positron emission tomography (PET). MRI widely used in can help exclude reversible causes memory problems but relatively low sensitivity differential subtypes.

Language: Английский

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Multifaceted roles of APOE in Alzheimer disease

Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: 20(8), P. 457 - 474

Published: June 21, 2024

Language: Английский

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Neuroinflammation in Alzheimer’s disease: insights from peripheral immune cells

Immunity & Ageing, Journal Year: 2024, Volume and Issue: 21(1)

Published: June 14, 2024

Abstract Alzheimer’s disease (AD) is a serious brain disorder characterized by the presence of beta-amyloid plaques, tau pathology, inflammation, neurodegeneration, and cerebrovascular dysfunction. The chronic neuroinflammation, breaches in blood-brain barrier (BBB), increased levels inflammatory mediators are central to pathogenesis AD. These factors promote penetration immune cells into brain, potentially exacerbating clinical symptoms neuronal death AD patients. While microglia, resident nervous system (CNS), play crucial role AD, recent evidence suggests infiltration cerebral vessels parenchyma peripheral cells, including neutrophils, T lymphocytes, B NK monocytes participate regulation immunity which expected huge future immunotherapy. Given this article seeks offer comprehensive overview their contributions neuroinflammation disease. Understanding these neuroinflammatory response vital for developing new diagnostic markers therapeutic targets enhance diagnosis treatment

Language: Английский

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Mechanistic insights and emerging therapeutic stratagems for Alzheimer’s disease

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 97, P. 102309 - 102309

Published: April 13, 2024

Language: Английский

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Evidence that Alzheimer’s Disease Is a Disease of Competitive Synaptic Plasticity Gone Awry

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: 99(2), P. 447 - 470

Published: April 23, 2024

Mounting evidence indicates that a physiological function of amyloid-β (Aβ) is to mediate neural activity-dependent homeostatic and competitive synaptic plasticity in the brain. I have previously summarized lines supporting this hypothesis highlighted similarities between Aβ anti-microbial peptides mediating cell/synapse competition. In cell competition, deploy multitude mechanisms ensure both self-protection competitor elimination. Here review recent studies showing similar are at play Aβ-mediated synapse competition perturbations these underpin Alzheimer’s disease (AD). Specifically, discuss ApoE, two crucial players AD, co-operate regulation Glial ApoE promotes by increasing production trophic monomeric inhibiting its assembly into toxic oligomers. Conversely, oligomers, once assembled, promote elimination synapses via direct activity amplification “eat-me” signals promoting weak synapses. further summarize neuronal may be part gene regulatory network normally plasticity, explaining selective vulnerability expressing neurons AD brains. Lastly, sleep key Aβ-orchestrated which not only induced but also required for underlining link AD. Together, results strongly argue gone awry, novel perspective research.

Language: Английский

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Apolipoprotein E in Alzheimer’s disease trajectories and the next-generation clinical care pathway

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(7), P. 1236 - 1252

Published: June 19, 2024

Language: Английский

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Brain inflammation co-localizes highly with tau in mild cognitive impairment due to early-onset Alzheimer’s disease

Brain, Journal Year: 2024, Volume and Issue: 148(1), P. 119 - 132

Published: July 16, 2024

Brain inflammation, with an increased density of microglia and macrophages, is important component Alzheimer's disease a potential therapeutic target. However, it incompletely characterized, particularly in patients whose begins before the age 65 years and, thus, have few co-pathologies. Inflammation has been usefully imaged translocator protein (TSPO) PET, but most inflammation PET tracers cannot image subjects low-binder TSPO rs6971 genotype. In development, participants any genotype can be novel tracer, 11C-ER176, that high binding more favourable metabolite profile than other currently available. We applied 11C-ER176 to detect brain mild cognitive impairment (MCI) caused by early-onset disease. Furthermore, we sought correlate localization volume loss, elevated amyloid-β (Aβ)and tau. studied 25 amnestic MCI (average 59 ± 4.5 years, 10 female) 23 healthy controls 6.0 12 female), both groups similar proportion all three TSPO-binding affinities. total distribution (VT), obtained arterial input function, was compared across using voxel-wise region-wise analyses. addition had Aβ (n = 23) tau 21). For tracers, standard uptake value ratios were calculated cerebellar grey matter as region reference. Regional correlations among determined. Data corrected for partial effect. Cognitive performance neuropsychological tools. disease, there default network, reaching statistical significance precuneus lateral temporal parietal association cortex bilaterally, right amygdala. Topographically, co-localized strongly (r 0.63 0.24). This correlation higher co-localization 0.55 0.25) (0.43 0.22). least atrophy (-0.29 0.26). These regional could detected polymorphisms. disease-related regions correlated impaired scores. Our data highlight importance target, process. they support notion that, shown experimental tissue animal models, propagation humans associated inflammation.

Language: Английский

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The Dual Role of Amyloid Beta-Peptide in Oxidative Stress and Inflammation: Unveiling Their Connections in Alzheimer’s Disease Etiopathology

Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1208 - 1208

Published: Oct. 8, 2024

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and it currently the seventh leading cause of death worldwide. It characterized by extracellular aggregation amyloid β-peptide (Aβ) into oligomers fibrils that synaptotoxicity neuronal death. Aβ exhibits dual role in promoting oxidative stress inflammation. This review aims to unravel intricate connection between these processes their contribution AD progression. The delves AD, focusing on involvement metals, mitochondrial dysfunction, biomolecule oxidation. distinct yet overlapping concept nitro-oxidative also discussed, detailing roles nitric oxide, perturbations, cumulative impact production neurotoxicity. Inflammation examined through astroglia microglia function, elucidating response within brain. blood-brain barrier oligodendrocytes are considered context pathophysiology. We current diagnostic methodologies emerging therapeutic strategies aimed at mitigating inflammation, thereby offering potential treatments for halting or slowing comprehensive synthesis underscores pivotal bridging advancing our understanding informing future research treatment paradigms.

Language: Английский

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