Nature Genetics, Journal Year: 2025, Volume and Issue: unknown
Published: March 17, 2025
Language: Английский
Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 157, P. 108241 - 108241
Published: Feb. 3, 2025
Language: Английский
Citations
0
The Journal of Prevention of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown, P. 100128 - 100128
Published: March 1, 2025
The swift rise in the prevalence of Alzheimer's disease (AD) alongside its significant societal and economic impact has created a pressing demand for effective interventions treatments. However, there are no available treatments that can modify progression disease. Eight AD brain tissues datasets three blood were obtained. Consensus clustering was utilized as method to discern various subtypes AD. Then, module genes screened using weighted correlation network analysis (WGCNA). Furthermore, screening hub conducted through machine-learning analyses. Finally, A comprehensive systematic approach druggable genome-wide Mendelian randomization (MR) conducted. Two subclasses identified, namely cluster.A cluster.B. levels gamma secretase activity, beta amyloid-beta 42 found be significantly elevated patients classified within cluster when compared those B. by utilizing differentially expressed shared among these clusters, along with identifying applying WGCNA subtypes, we able develop scoring system referred DG.score. This demonstrated remarkable predictive capability evaluated against multiple datasets. Besides, total 30 distinct may serve potential drug targets identified across at least one investigated, whether derived from samples or Among genes, specific candidates considered (LIMK2, MAPK8, NDUFV2) expression both tissues. our research also revealed association between LIMK2 concentrations CSF Aβ (OR 1.526 (1.155-2.018)), p-tau 1.106 (1.024-01.196)), hippocampal size 0.831 (0.702-0.948)). study provides notable advancement existing literature offering genetic evidence underscores therapeutic advantages focusing on gene treatment insight not only contributes understanding but guides future discovery efforts.
Language: Английский
Citations
0
Genes, Journal Year: 2025, Volume and Issue: 16(3), P. 331 - 331
Published: March 12, 2025
An apparent “inverse” relationship exists between two seemingly unconnected conditions, Alzheimer’s disease (AD) and cancer, despite sharing similar risk factors, like increased age obesity. AD is associated with amyloid beta (Aβ) plaques neurofibrillary tau tangles that cause neural degeneration; in contrast, characterized by enhanced cell survival proliferation. Apolipoprotein E (ApoE) the main lipoprotein found central nervous system via its high affinity receptors plays a critical role cholesterol transport uptake. ApoE has 3 protein isoforms, E2, E3, E4, respectively encoded for allelic variants of APOE (ε2, ε3, ε4). This review examines characteristics function described both cancer to assimilate evidence potential contribution mechanisms may underly reported inverse association conditions. Of genetic factors relevant most cases AD, well-known strongest APOE, specifically ε4 variant, whereas risk, not featured as significant contributor risk. However, at level contributes pathology affecting lipid physiology transport. In Aβ-dependent -independent interactions have been suggested, immunoregulation. Understanding mechanism action these diametrically opposed diseases enable differential targeting therapeutics provide beneficial outcome both.
Language: Английский
Citations
0
medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: March 11, 2025
ABSTRACT INTRODUCTION Hippocampal sclerosis of aging (HS-aging) is frequently present in individuals over 85 who die with dementia. Recent studies suggest that some loci associated Alzheimer’s disease (AD) may be more related to HS-aging. We aimed find AD-associated SNPs potentially METHODS assessed the relation AD polygenic risk score (AD-PRS) hippocampal subfield volumes by magnetic resonance imaging (MRI) as HS-by-proxy 1,130 non-demented participants. analyzed 1,708 associate their AD-PRS (83 variants) alongside RESULTS measures fimbria and body head show association AD-PRS, SHARPIN , GRN TNIP1 also after replication. replicated stronger presence HS-aging compared alone. DISCUSSION Results between AD-SNPs HS-proxy, enriched immune-brain axis pathways, differentiating from AD. This insight aids understanding interrelationships identifying specific therapeutic targets.
Language: Английский
Citations
0
Nature Genetics, Journal Year: 2025, Volume and Issue: unknown
Published: March 17, 2025
Language: Английский
Citations
0