Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: April 24, 2025
Language: Английский
Nature reviews. Neuroscience, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 19, 2025
Language: Английский
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Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)
Published: Feb. 26, 2025
Apolipoprotein E (APOE) has garnered significant attention as one of the most influential genetic risk factors for Alzheimer's disease (AD). While pathogenic role APOE4 in sporadic AD been extensively studied, research on protective effects APOE2 genotype and its underlying mechanisms remains limited. Additionally, existence sex differences ApoE2 continues to be a topic debate. In this study, we utilized humanized ApoE2- ApoE3- target replacement mice examine sex-specific cognition. Compared with female ApoE3 mice, found significantly lower spatial cognitive ability impaired hippocampal synaptic ultrastructure aged accompanied by reduced insulin signaling hippocampus. Further analyses metabolomics transcriptomic revealed that exhibit an age-related decline inositol levels, alterations levels signaling. Importantly, supplementation was alleviate peripheral glucose intolerance, enhance signaling, ultimately improve function. Interestingly, these were not observed between male mice. The findings only provide new insights into impact cognition but also offer strategy improvement through older women.
Language: Английский
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Ageing & Longevity, Journal Year: 2025, Volume and Issue: 2. 2025, P. 117 - 128
Published: Feb. 27, 2025
Amyloid precursor protein (APP) is central to Alzheimer's disease (AD) by its role in Aβ build-up and neuronal astrocytic malfunction. The major risk factor for late-onset AD aging, which increases APP processing both neurons astrocytes, consequently production. This focused review covers the subjects of how aging affect dynamics within cell types astrocytes dysfunction can enhance neuroinflammation injury. We discuss interplay between brains, where bi-directional cellular interactions accelerate neurodegeneration. Keywords: protein, Alzheimer`s disease, amyloid beta, neurons, neuroinflammation, reactive astrogliosis
Language: Английский
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Annals of Epidemiology, Journal Year: 2025, Volume and Issue: 104, P. 71 - 71
Published: March 12, 2025
Language: Английский
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CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(3)
Published: March 1, 2025
Alzheimer's disease (AD) involves a prolonged presymptomatic or preclinical stage with subtle pathological changes. Apolipoprotein E4 (APOE4) is significant genetic risk factor for AD, yet its specific role at the not fully understood. This study aimed to elucidate cellular and molecular effects of APOE4 compared APOE3 on AD progression during stage. We generated 5xFAD mice carrying human their non-AD controls. Behavioral tests, immunostaining, quantitative proteomics phosphoproteomics, Golgi staining, Western blotting were conducted 3 10 months age, respectively. Cell culture experiments performed assess APOE4's direct impact neuronal mitochondrial function. significantly increased β-amyloid (Aβ) deposition microglial activation in stage, without aggravating blood-brain barrier disruption. Proteomic biochemical analysis revealed strong features synaptic degeneration dysfunction associated APOE4. Notably, promoted fusion mitophagy while inhibiting fission, leading impaired energy supply reactive oxygen species. Our findings indicate that accelerates pathologies by exacerbating Aβ deposition, neuroinflammation, degeneration. The highlights as critical mediator APOE4-induced progression, providing potential targets early intervention.
Language: Английский
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Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(3), P. 200 - 200
Published: March 18, 2025
The rising prevalence of Alzheimer’s disease (AD), particularly among older adults, has driven increased research into its underlying mechanisms and risk factors. Aging, genetic susceptibility, cardiovascular health are recognized contributors to AD, but how the age onset affects progression remains underexplored. This study investigates role early- versus late-onset (EOAD LOAD, respectively) in shaping trajectory cognitive decline. Leveraging data from Religious Orders Study Memory Aging Project (ROSMAP), two cohorts were established: individuals with early-onset AD those AD. Comprehensive analyses, including differential gene expression profiling, pathway enrichment, co-expression network construction, conducted identify distinct molecular signatures associated each cohort. Network modularity learning algorithms used discern inner structure networks their related functional features. Computed descriptors provided deeper insights influence at on biological
Language: Английский
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Translational Neurodegeneration, Journal Year: 2025, Volume and Issue: 14(1)
Published: March 26, 2025
Abstract Traumatic brain injury (TBI) has emerged as a significant risk factor for Alzheimer’s disease (AD), complex and devastating neurodegenerative disorder characterized by progressive cognitive decline memory loss. Both conditions share common feature: blood‒brain barrier (BBB) dysfunction, which is believed to play pivotal role in linking TBI the development of AD. This review delves into intricate relationship between AD, with focus on BBB dysfunction its critical mechanisms therapeutic development. We first present recent evidence from epidemiological studies highlighting increased incidence AD among individuals history TBI, well pathological animal model that demonstrate how can accelerate AD-like pathology. Next, we explore may mediate TBI-induced Finally, investigate shared molecular pathways associated both discuss latest findings targeting these employing regenerative approaches, such stem cell therapy pharmacological interventions, enhance function mitigate neurodegeneration.
Language: Английский
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Journal of Neuropathology & Experimental Neurology, Journal Year: 2025, Volume and Issue: unknown
Published: March 29, 2025
Abstract Cerebral amyloid angiopathy (CAA) is a common feature of Alzheimer’s disease in which amyloid-β (Aβ) deposits cerebral and leptomeningeal vessel walls, predisposing vessels to micro- macro-hemorrhages. The walls contain distinct proteins heparan sulfate (HS), yet how vascular HS jointly associate with Aβ unknown. We conducted the first multi-omics study systematically characterize as well abundance, sulfation level, disaccharide composition leptomeninges from 23 moderate severe CAA cases controls. then analyzed associations between other proteins, HS, apolipoprotein E genotype. found an increase minor containing unsubstituted glucosamine, 6-O sulfated disaccharides; Aβ40 levels positively correlated glucosamine. There was also extracellular derived brain parenchyma or plasma, including olfactomedin-like protein 3, fibrinogen, serum protein, E, secreted frizzled related protein-3. Our findings alterations specific CAA-affected provide molecular insight into remodeling that co-occurs may indicate basis for antemortem diagnostic assay development therapeutic strategies impede Aβ-HS interactions.
Language: Английский
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PLoS Genetics, Journal Year: 2025, Volume and Issue: 21(4), P. e1011407 - e1011407
Published: April 9, 2025
Genome-wide association studies have identified thousands of common variants associated with an increased risk neurodegenerative disorders. However, the noncoding localization these has made assignment target genes for brain cell types challenging. Genomic approaches that infer chromosomal 3D architecture can link and distal gene regulatory elements such as enhancers to promoters. By using enhancer-to-promoter interactome maps human microglia, neurons, oligodendrocytes, we cell-type-specific enrichment genetic heritability disorders through stratified linkage disequilibrium score regression. Our analysis suggests multiple is enriched at microglial chromatin contact sites, while schizophrenia predominantly sites in neurons followed by oligodendrocytes. Through Hi-C coupled multimarker genomic annotation (H-MAGMA), disease Alzheimer’s disease, Parkinson’s sclerosis, amyotrophic lateral sclerosis schizophrenia. We found disease-risk were overrepresented microglia compared other across conditions within Notably, pathways largely specific each disease. findings reinforce important, genetically informed type therapeutic interventions highlight potentially targetable disease-relevant pathways.
Language: Английский
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Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(4)
Published: April 1, 2025
Effect of apolipoprotein E (APOE) on Alzheimer's disease and related dementias (ADRD) risk is heterogeneous across populations, with scarce data Hispanics/Latinos. APOE genotype was studied in 12,221 Hispanics/Latinos (per cohort via metanalysis): Caribbean-Hispanics, Mexicans, Mexican-Americans, Peruvians/Bolivians. A subsample had longitudinal assessment plasma p-tau. We tested the modifying effects global local ancestries. Results were replicated an independent Peruvian brain samples. ε4 effect strongest Peruvians/Bolivians (odds ratio [OR] = 6.13, 95% confidence interval [CI] 2.71-13.83), followed by Mexicans (OR 4.31, CI 1.58-11.74), Mexican-Americans 3.06, 2.04-4.59), Caribbean-Hispanics 2.22, 1.99-2.48). Meta-analyses showed OR 2.32 (95% 2.09-2.57) 0.81 0.68-0.97) for ε2 allele, respectively. The independently Peruvians 5.06, 2.48-10.70). carriers displayed higher ADRD conversions p-tau levels. Global ancestries did not modify risk, they associated Braak stage. shows a our sample, largest to date. stronger than other Hispanic/Latino groups. strong size Bolivians second cohort. Meta-analysis confirmed significant association (ADRD). ancestry do between ADRD.
Language: Английский
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