Synapse vulnerability and resilience underlying Alzheimer’s disease

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

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Integrative Analysis of Metabolome and Proteome in the Cerebrospinal Fluid of Patients with Multiple System Atrophy

Cells, Journal Year: 2025, Volume and Issue: 14(4), P. 265 - 265

Published: Feb. 12, 2025

Multiple system atrophy (MSA) is a progressive neurodegenerative synucleinopathy. Differentiating MSA from other synucleinopathies, especially in the early stages, challenging because of its overlapping symptoms with forms Parkinsonism. Thus, there pressing need to clarify underlying biological mechanisms and identify specific biomarkers for MSA. The metabolic profile cerebrospinal fluid (CSF) known be altered To further investigate behind changes, we created network CSF metabolites patients analysed these changes using bioinformatic software. Acknowledging limitations metabolomics, incorporated proteomic data improve overall comprehensiveness study. Our silico predictions showed elevated ROS, cytoplasmic inclusions, white matter demyelination, ataxia, neurodegeneration, ATP concentration, neurotransmitter release, oligodendrocyte count predicted suppressed samples. Machine learning dimension reduction are important multi-omics approaches as they handle large amounts data, patterns, make while reducing variance without information loss generating easily visualised plots that help clusters, or outliers. integrated multiomics machine essential elucidating identifying potential diagnostic

Language: Английский

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Design, synthesis of 2-phenyl-1H-benzo[d]imidazole derivatives as 17β-HSD10 inhibitor for the treatment of Alzheimer's Disease

RSC Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

It has been reported that 17β-HSD10 plays a key role in Alzheimer's disease. Here, total of 44 2-phenyl-1H-benzo[d]imidazole derivatives were designed and synthesized as novel inhibitors based on rational design SAR studies. Among them, compound 33 (N-(4-(1,4,6-trimethyl-1H-benzo[d] imidazol-2-yl)phenyl)cyclohexanecarboxamide) showed high inhibitory efficacy (17β-HSD10 IC50 = 1.65 ± 0.55 μM) low toxicity (HepaRG >100 μM). The Morris water maze experiment revealed could alleviate cognitive impairment induced by scopolamine mice. This study facilitates the further development more potent for treatment

Language: Английский

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The Transdiagnostic Value of Plasma Biomarkers for Neurodegenerative and Cerebrovascular MRI Findings

Neurology, Journal Year: 2025, Volume and Issue: 104(7)

Published: March 10, 2025

Language: Английский

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Cognitive Frailty: A Comprehensive Clinical Paradigm Beyond Cognitive Decline

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102738 - 102738

Published: March 1, 2025

Language: Английский

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Biological Function Analysis of MicroRNAs and Proteins in the Cerebrospinal Fluid of Patients with Parkinson’s Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13260 - 13260

Published: Dec. 10, 2024

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by alpha-synuclein aggregation into Lewy bodies in the neurons. Cerebrospinal fluid (CSF) considered most suited source for investigating PD pathogenesis and identifying biomarkers. While microRNA (miRNA) profiling can aid investigation of post-transcriptional regulation diseases, information on miRNAs CSF patients with remains limited. This review combines miRNA analysis proteomic to explore collective impact mechanisms PD. We constructed separate networks altered proteomes using bioinformatics method. Altered were poorly linked biological functions owing limited information; however, changes protein expression strongly associated functions. Subsequently, integrated further analysis. In silico prediction from network revealed relationships between proteins, highlighting increased reactive oxygen species generation, neuronal loss, neurodegeneration suppressed ATP synthesis, mitochondrial function, neurotransmitter release The approach suggests potential as biomarkers critical underlying combined strategy could enhance our understanding complex biochemical support development diagnostic therapeutic strategies precision medicine.

Language: Английский

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Morphometric Similarity Patterning of Amyloid-β and Tau Proteins Correlates with Transcriptomics in the Alzheimer’s Disease Continuum

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12871 - 12871

Published: Nov. 29, 2024

Bridging the gap between cortical morphometric remodeling and gene expression can help to clarify effects of selective brain accumulation Amyloid-β (Aβ) tau proteins occurring in Alzheimer's disease (AD). To this aim, we derived similarity (MS) networks from 126 Aβ- tau-positive (Aβ+/tau+) 172 Aβ-/tau- subjects, investigated association group-wise regional MS differences transcriptional correlates thanks an imaging transcriptomics approach grounded Allen Human Brain Atlas (AHBA). The expressed with highest correlation alterations was

Language: Английский

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