Biomedical Signal Processing and Control, Journal Year: 2025, Volume and Issue: 109, P. 107926 - 107926
Published: May 6, 2025
Language: Английский
Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)
Published: April 8, 2024
Abstract Some individuals are able to maintain their cognitive abilities despite the presence of significant Alzheimer’s Disease (AD) neuropathological changes. This discrepancy between cognition and pathology has been labeled as resilience evolved into a widely debated concept. External factors such stimulation associated with AD, but exact cellular molecular underpinnings not completely understood. In this review, we discuss current definitions used in field, highlight translational approaches investigate AD summarize underlying substrates that have derived from human animal studies, which received more attention last few years. From these studies picture emerges resilient different patients terms specific pathological species reaction pathology, possibly helps up certain tipping point. Studying rare can be great importance it could pave way novel therapeutic avenues for AD.
Language: Английский
Citations
21
Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 147(1)
Published: Jan. 4, 2024
Abstract Tau hyperphosphorylation and aggregation is a common feature of many dementia-causing neurodegenerative diseases. can be phosphorylated at up to 85 different sites, there increasing interest in whether tau phosphorylation specific epitopes, by kinases, plays an important role disease progression. The AMP-activated protein kinase (AMPK)-related enzyme NUAK1 has been identified as potential mediator pathology, whereby NUAK1-mediated Ser356 prevents the degradation proteasome, further exacerbating accumulation. This study provides detailed characterisation association p-tau with progression Alzheimer’s identifying Braak stage-dependent increase levels almost ubiquitous presence neurofibrillary tangles. We also demonstrate, using sub-diffraction-limit resolution array tomography imaging, that co-localises synapses AD postmortem brain tissue, evidence this form may play roles To assess impacts pharmacological NUAK inhibition ex vivo system retains multiple cell types brain-relevant neuronal architecture, we treated postnatal mouse organotypic slice cultures from wildtype or APP/PS1 littermates commercially available NUAK1/2 inhibitor WZ4003. Whilst were no genotype-specific effects, found WZ4003 results culture-phase-dependent loss total Ser356, which corresponds reduction synaptic proteins. By contrast, application live human lowering alongside increased tubulin protein. work identifies differential responses adult will consider future developing tau-targeting therapeutics for disease.
Language: Английский
Citations
18
Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)
Published: May 7, 2024
Abstract Background Alzheimer’s disease (AD) is a prevalent form of dementia leading to memory loss, reduced cognitive and linguistic abilities, decreased self-care. Current AD treatments aim relieve symptoms slow progression, but cure elusive due limited understanding the underlying mechanisms. Main content Stem cell technology has potential revolutionize research. With ability self-renew differentiate into various types, stem cells are valuable tools for modeling, drug screening, therapy. Recent advances have broadened our beyond deposition amyloidβ (Aβ) or tau proteins in encompass risk genes, immune system disorders, neuron–glia mis-communication, relying heavily on cell-derived models. These cell-based models (e.g., organoids microfluidic chips) simulate vivo pathological processes with extraordinary spatial temporal resolution. technologies alleviate pathology through pathways, including immunomodulation, replacement damaged neurons, neurotrophic support. In recent years, transplantation glial like oligodendrocytes infusion exosomes become hot research topics. Conclusion Although therapies face several challenges, such as extended culture time low differentiation efficiency, they still show considerable treatment likely preferred
Language: Английский
Citations
13
EBioMedicine, Journal Year: 2025, Volume and Issue: 112, P. 105557 - 105557
Published: Jan. 31, 2025
Synapse preservation is key for healthy cognitive ageing, and synapse loss represents a critical anatomical basis of dysfunction in Alzheimer's disease (AD), predicting dementia onset, severity, progression. viewed as primary pathologic event, preceding neuronal brain atrophy AD. Synapses may, therefore, represent one the earliest clinically most meaningful targets neuropathologic processes driving AD dementia. The highly selective particularly vulnerable synapses while leaving others, termed resilient, largely unaffected. Yet, anatomic molecular hallmarks resilient populations their association with changes (e.g. amyloid-β plaques tau tangles) memory remain poorly understood. Characterising selectively may be to understanding mechanisms versus enable development robust biomarkers disease-modifying therapies
Language: Английский
Citations
1
Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown, P. e00540 - e00540
Published: Feb. 1, 2025
Astrocytes and oligodendrocytes, once considered passive support cells, are now recognized as active participants in the pathogenesis of Alzheimer's disease. Emerging evidence highlights critical role that these glial cells play pathological features Alzheimer's, including neuroinflammation, excitotoxicity, synaptic dysfunction, myelin degeneration, which contribute to neurodegeneration cognitive decline. Here, we review current understanding astrocyte oligodendrocyte pathology disease highlight research supports therapeutic potential modulating functions treat
Language: Английский
Citations
1
Cells, Journal Year: 2023, Volume and Issue: 12(24), P. 2824 - 2824
Published: Dec. 12, 2023
The greatest risk factor for neurodegeneration is the aging of multiple cell types human CNS, among which microglia are important because they "sentinels" internal and external perturbations have long lifespans. We aim to emphasize microglial signatures in physiologic brain Alzheimer's disease (AD). A systematic literature search all published articles about senescence healthy AD was performed, searching PubMed Scopus online databases. Among 1947 screened, a total 289 were assessed full-text eligibility. Microglial transcriptomic, phenotypic, neuropathological profiles analyzed comprising AD. Our review highlights that studies on animal models only partially clarify what happens humans. Human mice hugely heterogeneous. Like two-sided coin, can be protective or harmful, depending context. Brain health depends upon balance between actions reactions maintaining homeostasis cooperation with other (especially astrocytes oligodendrocytes). During aging, accumulating oxidative stress mitochondrial dysfunction weaken leading dystrophic/senescent, otherwise over-reactive, phenotype-enhancing neurodegenerative phenomena. Microglia crucial managing Aβ, pTAU, damaged synapses, being pivotal pathogenesis.
Language: Английский
Citations
12
JCI Insight, Journal Year: 2024, Volume and Issue: 9(14)
Published: July 21, 2024
The aggregation and prion-like propagation of tau are the hallmarks Alzheimer's disease (AD) other tauopathies. However, molecular mechanisms underlying assembly spread pathology remain elusive. Epidemiological data show that exposure to fine particulate matter (PM2.5) is associated with an increased risk AD. unknown. Here, we showed PM2.5 triggered promoted formation fibrils. Injection PM2.5-induced preformed fibrils (PFFs) into hippocampus P301S transgenic mice induced cognitive deficits synaptic dysfunction. Furthermore, intranasal administration exacerbated impairment in mice. In conclusion, our results indicated impairments. These provide mechanistic insight how increases
Language: Английский
Citations
4
Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 148(1)
Published: Aug. 5, 2024
Abstract Asymptomatic Alzheimer’s disease (AsymAD) describes the status of individuals with preserved cognition but identifiable (AD) brain pathology (i.e., beta-amyloid (Aβ) deposits, neuritic plaques, and neurofibrillary tangles) at autopsy. In this study, we investigated postmortem brains a cohort AsymAD subjects to gain insight into mechanisms underlying resilience AD cognitive decline. Our results showed that cases exhibit enrichment in core decreased filamentous plaque accumulation, increased plaque-surrounding microglia. Less pathological tau aggregation dystrophic neurites was found than brains, seeding activity comparable healthy brains. We used spatial transcriptomics characterize niche further revealed autophagy, endocytosis, phagocytosis as pathways associated genes upregulated niche. Furthermore, levels ARP2 CAP1, which are actin-based motility proteins participate dynamics actin filaments allow cell motility, were microglia surrounding amyloid plaques cases. findings suggest amyloid-plaque microenvironment is characterized by presence highly efficient compared These two can potentially protect against toxic cascade initiated Aβ, preserving health, slowing progression.
Language: Английский
Citations
4
Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 104, P. 102638 - 102638
Published: Dec. 12, 2024
Language: Английский
Citations
4
Trends in Neurosciences, Journal Year: 2023, Volume and Issue: 47(2), P. 135 - 149
Published: Dec. 20, 2023
Language: Английский
Citations
10