Serum proteomics reveals early biomarkers of Alzheimer's disease: The dual role of <i>APOE-ε4 </i>

BioScience Trends, Journal Year: 2025, Volume and Issue: 19(1), P. 1 - 9

Published: Jan. 22, 2025

Alzheimer's disease (AD), the leading cause of dementia, significantly impacts global public health, with cases expected to exceed 150 million by 2050. Late-onset (LOAD), predominantly influenced APOE-ε4 allele, exhibits complex pathogenesis involving amyloid-β (Aβ) plaques, neurofibrillary tangles (NFTs), neuroinflammation, and blood-brain barrier (BBB) disruption. Proteomics has emerged as a pivotal technology in uncovering molecular mechanisms identifying biomarkers for early diagnosis intervention AD. This paper reviews genetic roles pathology AD, including its effects on Aβ aggregation, tau phosphorylation, BBB integrity. Additionally, it highlights recent advances serum proteomics, revealing APOE-ε4-dependent independent protein signatures potential Despite technological progress, challenges such population diversity, standardization, distinguishing AD-specific remain. Directions future research emphasize multicenter longitudinal studies, multi-omics integration, clinical translation proteomic findings enable detection AD personalized treatment strategies. hold promise improving patient outcomes reducing burden.

Language: Английский

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<i>N⁵</i>-((perfluorophenyl)amino)glutamine regulates BACE1, tau phosphorylation, synaptic function, and neuroinflammation in Alzheimer's disease models

BioScience Trends, Journal Year: 2025, Volume and Issue: 19(1), P. 102 - 115

Published: Jan. 24, 2025

Alzheimer's disease (AD) is the most common type of dementia. Its incidence rising rapidly as global population ages, leading to a significant social and economic burden. AD involves complex pathologies, including amyloid plaque accumulation, synaptic dysfunction, neuroinflammation. This study explores therapeutic potential N 5 -((perfluorophenyl)amino)glutamine (RA-PF), derivative γ-glutamyl-N'-(2-hydroxyphenyl)hydrazide (Ramalin), compound with antioxidant anti-inflammatory properties. Administration RA-PF 5xFAD mice decreases BACE1, reduces Aβ deposition, inhibits microglial activation, restores transmission, improves mitochondrial motility, recovery cognitive function. Additionally, treatment in 3xTg-AD alleviates anxiety-like behaviors, tau phosphorylation via inactivating GSK-3β, BACE1 expression. Further transcriptomic analysis reveals models recovers phagosome, inflammation, NOD-like receptor, presynaptic membrane, postsynaptic membrane related signaling pathways. These findings suggest that effectively targets multiple aspects pathology, offering novel multi-target approach for treatment.

Language: Английский

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The potential and challenges of TREM2-targeted therapy in Alzheimer’s disease: insights from the INVOKE-2 study

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: April 25, 2025

Alzheimer’s disease (AD) is a severe neurodegenerative disorder with growing global burden. With the rising incidence of AD, need for novel therapeutic targets has become increasingly critical. TREM2, receptor expressed on microglial cells, plays crucial role in modulating neuroinflammation and clearing pathological substrates, making it promising candidate AD therapy. However, recent clinical trial INVOKE-2 failed to demonstrate significant benefits TREM2-targeted antibody AL002, raising doubts about efficacy methods. This article examines TREM2 pathogenesis, evaluates potential reasons disappointing outcomes trial, discusses future directions TREM2-based therapies. Factors such as treatment timing, dosage optimization, patient genetic variability, combination therapy strategies are identified critical determinants success. Future studies should aim refine strategies, identify precise indications, explore therapies enhance efficacy.

Language: Английский

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Agarwood as a potential therapeutic for Alzheimer's disease: Mechanistic insights and target identification

Drug Discoveries & Therapeutics, Journal Year: 2024, Volume and Issue: 18(6), P. 375 - 386

Published: Dec. 20, 2024

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and functional impairments. Despite extensive research, its pathogenesis remains incompletely understood, effective treatments are limited. This study explored the therapeutic potential of agarwood in AD integrating network pharmacology, protein-protein interaction (PPI) analysis, single-cell expression analysis. The results revealed that compounds may modulate key inflammatory genes such as NFKB1, STAT1, TLR4, alleviating neuroinflammation; enhance HSP90 regulate KDR signaling to improve blood-brain barrier (BBB) integrity; promote activity PTPN11 CXCR4 support oligodendrocyte precursor cell (OPC) repair remyelination. Single-cell analysis highlighted cell-type-specific patterns, particularly OPCs endothelial cells, underscoring their relevance pathology. Agarwood's multi-dimensional positions it promising candidate for development novel treatments.

Language: Английский

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