Mechanistic Intimate Insights into the Role of Hydrogen Sulfide in Alzheimer’s Disease: A Recent Systematic Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15481 - 15481

Published: Oct. 23, 2023

In the rapidly evolving field of Alzheimer's Disease (AD) research, intricate role Hydrogen Sulfide (H

Language: Английский

---

Enrichment of infection-associated bacteria in the low biomass brain bacteriota of Alzheimer’s disease patients

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(2), P. e0296307 - e0296307

Published: Feb. 9, 2024

Alzheimer’s disease (AD) is a neurodegenerative accompanied by neuroimmune inflammation in the frontal cortex and hippocampus. Recently, presence of bacteria AD-affected brains has been documented, prompting speculation about their potential role AD-associated neuroinflammation. However, characterization bacteriota human affected AD remains inconclusive. This study aimed to investigate associations between specific pathology examining brain tissues from regions (frontal hippocampus) non-AD-associated hypothalamus. Employing 16S rRNA gene sequencing, 30 postmortem tissue samples four individuals with normal histology (N) patients were analyzed, along three blank controls. A remarkably low biomass characterized bacteriota, overall structures delineated primarily rather than AD. While most analyzed parameters exhibited no significant distinction N groups, unique detection Cloacibacterium normanense stood out. Additionally, infection-associated bacteria, as opposed periodontal pathogens, notably enriched brains. study’s findings provide valuable insights into link bacterial infection neuroinflammation

Language: Английский

---

Parallel electrophysiological abnormalities due to COVID‐19 infection and to Alzheimer's disease and related dementia

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 29, 2024

Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting "brain fog" and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include slowing (reduced alpha rhythm; increased slow waves) epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that deficits due COVID-19 Alzheimer's related dementia (ADRD) are driven by overlapping pathologies neurophysiological abnormalities. seen in patients resemble those observed early stages neurodegenerative diseases, particularly ADRD. It is proposed similar Long COVID ADRD parallel neuroinflammation, astrocyte reactivity, hypoxia, neurovascular injury. These underpinning decline can be detected routine exams. Future research will explore value monitoring for predicting long-term outcomes efficacy therapeutic interventions. HIGHLIGHTS: Abnormal intrinsic electrophysiological brain activity, such as EEG, reduced wave, characteristic findings patients. have potential neural biomarkers identify neurological complications at stage disease, assist clinical assessment, assess risk Similar typically with impairments, Evidence presented supports idea resulting, least part, from neuroinflammatory mechanisms reactivity. Identifying common biological highlight critical underlying disorders decline. elucidates questions regarding impairment not yet been adequately investigated.

Language: Английский

---

Senescent brain cell types in Alzheimer's disease: Pathological mechanisms and therapeutic opportunities

Neurotherapeutics, Journal Year: 2025, Volume and Issue: 22(3), P. e00519 - e00519

Published: Jan. 6, 2025

Cellular senescence is a cell state triggered by programmed physiological processes or cellular stress responses. Stress-induced senescent cells often acquire pathogenic traits, including toxic secretome and resistance to apoptosis. When form faster than they are cleared the immune system, accumulate in tissues throughout body contribute age-related diseases, neurodegeneration. This review highlights evidence of brain their role Alzheimer's disease (AD), leading cause dementia older adults. We also discuss progress challenges senotherapies, pharmacological strategies clear mitigate effects, which hold promise as interventions for AD related dementias (ADRD).

Language: Английский

---

Cortical thickness correlated with peripheral inflammatory cytokines in amyotrophic lateral sclerosis

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: Jan. 7, 2025

Amyotrophic lateral sclerosis (ALS) is a rare, devastating neurodegenerative disease that affects upper and lower motor neurons, resulting in muscle atrophy, spasticity, hyperreflexia, paralysis. Inflammation plays an important role the development of ALS, associated with rapid progression. Current observational studies indicate thinning cortical thickness patients ALS progression cognitive changes. However, effects inflammatory cytokines on are unclear. Here, we investigated relationship between ALS. We evaluated 51 for including interleukin (IL)-4, interferon (IFN)-α, IL-1β, IL-2, IL-5, IL-12, tumor necrosis factor (TNF)-α, IL-6, IL-10, IL-8, IL-17, IFN-γ analyzed correlation these indicators functional rating scale-revised (ALSFRS-R) score or rate (ΔFS score). Twenty-six 26 controls were studied using whole-cortex analysis, post-hoc analyses performed to examine brain ALSFRS-R ΔFS scores. IL-4, IFN-α, IL-2 levels significantly correlated scores, level was After controlling age sex, group had thinner cortexes multiple clusters across than control group. Further revealed right superior temporal lingual gyrus regions inversely There significant positive cortex level. These results suggest reduced non-motor areas. Inflammatory factors (especially IL-2) thickness, both related rate, suggesting

Language: Английский

---

Alzheimer’s Disease: Exploring Pathophysiological Hypotheses and the Role of Machine Learning in Drug Discovery

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1004 - 1004

Published: Jan. 24, 2025

Alzheimer’s disease (AD) is a major neurodegenerative dementia, with its complex pathophysiology challenging current treatments. Recent advancements have shifted the focus from traditionally dominant amyloid hypothesis toward multifactorial understanding of disease. Emerging evidence suggests that while amyloid-beta (Aβ) accumulation central to AD, it may not be primary driver but rather part broader pathogenic process. Novel hypotheses been proposed, including role tau protein abnormalities, mitochondrial dysfunction, and chronic neuroinflammation. Additionally, gut–brain axis epigenetic modifications gained attention as potential contributors AD progression. The limitations existing therapies underscore need for innovative strategies. This study explores integration machine learning (ML) in drug discovery accelerate identification novel targets candidates. ML offers ability navigate AD’s complexity, enabling rapid analysis extensive datasets optimizing clinical trial design. synergy between these themes presents promising future more effective

Language: Английский

---

Antagonizing Il10 and Il4 signaling via intracerebral decoy receptor expression attenuates Aβ accumulation

Acta Neuropathologica Communications, Journal Year: 2025, Volume and Issue: 13(1)

Published: March 7, 2025

Abstract Multiple lines of evidence indicate that immune signaling can impact the pathological progression in Alzheimer’s disease (AD), including amyloid deposition, tau aggregation, synaptic pathology and neurodegenerative trajectory. In earlier studies, we reported intracerebral expression anti-inflammatory cytokines, Interleukin-10 (Il10) Interleukin-4 (Il4), increased β (Aβ) burden TgCRND8 mice, a preclinical model AD-type amyloidosis. As both receptor (IL10R) (IL4R) are upregulated an age-progressive manner rodent models AD specific regions human brains, hypothesized decoy strategy specifically targeting Il10 Il4 could have disease-modifying effect. We derivatized ectodomains mouse Il10R (sIl10R) Il4R (sIl4R) into corresponding recombinant solubilized forms delivered these intracranially neonatal mice or hippocampally adult with pre-existing Aβ deposits. AAV-mediated sIl10R sIl4R robustly attenuated when expressed neonatally while hippocampus injection cohort, AAV-sIl4R, but not sIl10R, reduced burden. had opposing effects on microglial astrocyte proliferation, generally reducing gliosis. RNAseq analysis showed likely acts as checkpoint inhibitor show unexpected impacts genes related to circadian rhythm. Notably, neither nor altered two transgenic models, despite robust glial proliferation. Together, data reveal mediated physiological beneficially deposition thus represent novel immunomodulatory approaches for therapy.

Language: Английский

---

Altered triple network model connectivity is associated with cognitive function and depressive symptoms in older adults

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(3)

Published: March 1, 2025

Late-life cognitive impairment and depression frequently co-occur share many symptoms. However, the specific neural clinical factors contributing to both their common distinct profiles in older adults remain unclear. We investigated resting-state correlates of depressive symptoms (n = 248 n 95) using clinical, blood, neuroimaging data. computed a connectivity matrix across default mode, executive control, salience networks. Cross-validated elastic net regression identified features reflecting function These were validated on held-out dataset. discovered that white matter hyperintensities nine overlapping nodes spanning all three networks are associated with symptoms, including left amygdala, hippocampus, bilateral ventral tegmental area. Our findings reveal intertwined influencing late life, offering insights into shared characteristics potential therapeutic targets. Resting-state markers decline late-life depression. Symptom-associated alterations present major brain interest, salience, control Some regions interest

Language: Английский

---

Role of toll-like receptors in post-COVID-19 associated neurodegenerative disorders?

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: March 26, 2025

In the intricate realm of interactions between hosts and pathogens, Toll-like receptors (TLRs), which play a crucial role in innate immune response, possess ability to identify specific molecular signatures. This includes components originating from pathogens such as SARS-CoV-2, well resulting damage-associated patterns (DAMPs), endogenous molecules released after cellular damage. A developing perspective suggests that TLRs central neuroinflammation, fundamental factor neurodegenerative conditions like Alzheimer’s Parkinson’s disease (PD). comprehensive review consolidates current research investigating potential interplay TLRs, their signaling mechanisms, processes neurodegeneration following SARS-CoV-2 infection with an aim elucidate involvement long-term neurological complications COVID-19 explore targeting means implementing intervention strategies for prevention or treatment COVID-19-associated brain outcomes.

Language: Английский

---

Immune modulation to treat Alzheimer’s disease

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 31, 2025

Abstract Immune mechanisms play a fundamental role in Alzheimer’s disease (AD) pathogenesis, suggesting that approaches which target immune cells and immunologically relevant molecules can offer therapeutic opportunities beyond the recently approved amyloid beta monoclonal therapies. In this review, we provide an overview of immunomodulatory therapeutics development, including their preclinical evidence clinical trial results. Along with detailing processes involved AD pathogenesis highlighting how these be therapeutically targeted to modify progression, summarize knowledge gained from previous trials immune-based interventions, series recommendations for development future treat AD.

Language: Английский

---