Nature Communications, Год журнала: 2025, Номер 16(1)
Опубликована: Апрель 24, 2025
Язык: Английский
Microorganisms, Год журнала: 2025, Номер 13(1), С. 90 - 90
Опубликована: Янв. 5, 2025
For decades, Alzheimer's Disease (AD) research has focused on the amyloid cascade hypothesis, which identifies amyloid-beta (Aβ) as primary driver of disease. However, consistent failure Aβ-targeted therapies to demonstrate efficacy, coupled with significant safety concerns, underscores need rethink our approach AD treatment. Emerging evidence points microbial infections environmental factors in pathoetiology. Although a definitive causal link remains unestablished, collective is compelling. This review explores unconventional perspectives and emerging paradigms regarding involvement pathogenesis, emphasizing gut-brain axis, brain biofilms, oral microbiome, viral infections. Transgenic mouse models show that gut microbiota dysregulation precedes Aβ accumulation, signaling pathways. Viral like Herpes Simplex Virus Type 1 (HSV-1) Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may lead by modulating host processes immune system. peptide's antimicrobial function response infection might inadvertently promote AD. We discuss potential microbiome-based promising strategies for managing potentially preventing progression. Fecal transplantation (FMT) restores balance, reduces improves cognition preclinical models. Probiotics prebiotics reduce neuroinflammation plaques, while antiviral targeting HSV-1 vaccines shingles vaccine mitigate pathology. Developing effective treatments requires standardized methods identify measure patients, enabling personalized address individual contributions pathogenesis. Further needed clarify interactions between microbes Aβ, explore bacterial interplay, understand their broader effects translate these insights into clinical interventions.
Язык: Английский
Процитировано
3
Brain, Год журнала: 2025, Номер unknown
Опубликована: Янв. 16, 2025
Abstract The APOE4 allele is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD). While strongly associated with amyloid-beta (Aβ), its relationship tau accumulation less understood. Studies evaluating role of on showed conflicting results, particularly regarding independence these associations from Aβ load. In this study, we examined three independent longitudinal cohorts (BioFINDER-1, BioFINDER-2 and WRAP) in which participants had cross-sectional measures tangles (tau-PET; temporal meta-ROI entorhinal) or soluble p-tau (p-tau217), Aβ-PET APOE genotype. study included a total 1370 cognitively unimpaired (CU) 449 mild cognitive impairment (MCI) subjects, followed longitudinally tau-PET p-tau217. carriers accounted 40.2-50% cohorts. Different linear regressions (cross-sectional) mixed-effect models (longitudinal) as outcomes were fitted to test effect predictor, well combination baseline load (including interaction). All age, sex status covariates. We found no effects carriership insoluble either cohort (BioFINDER-2 WRAP), both meta-ROI, when was present model (p=0.531-0.949). alone best predictor accumulation, interaction between tau-PET. BioFINDER-2, there significant (b=0.166, p<0.001) entorhinal cortex at baseline. However, not WRAP PET. No (p=0.683-0.708) (p=0.188-0.570) p-tau217 observed BioFINDER-1 WRAP. Similarly, observed. Mediation analysis revealed that fully mediated most (46-112%, p-tau217). largest (BioFINDER-2), looking groups by number ε4 alleles, an homozygotes levels over time while only conclusion, although aggregation, it seems be minimally changes given level pathology, confirming primacy driving pathology.
Язык: Английский
Процитировано
2
Cells, Год журнала: 2025, Номер 14(3), С. 168 - 168
Опубликована: Янв. 22, 2025
The recent approval of lecanemab highlights that the amyloid beta (Aβ) protein is an important pathological target in Alzheimer’s disease (AD) and further emphasizes significance neuroinflammatory pathways regulating Aβ accumulation. Indeed, accumulation triggers microglia activation, which are key mediators neuroinflammation. inflammatory responses this process can lead to neuronal damage functional decline. Microglia secrete proinflammatory cytokines accelerate death release anti-inflammatory growth factors contributing recovery protection. Thus, play a dual role neurodegeneration neuroprotection, complicating their function AD. Therefore, elucidating complex interactions between protein, microglia, neuroinflammation essential for developing new strategies treating This review investigates receptors involved activating aims enhance understanding how these processes impact AD, as well they be regulated. also analyzed studies reported existing literature ongoing clinical trials. Overall, will contribute regulatory mechanisms therapies slow progression
Язык: Английский
Процитировано
1
Cell Genomics, Год журнала: 2025, Номер unknown, С. 100763 - 100763
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
1
Trends in Molecular Medicine, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 1, 2024
Язык: Английский
Процитировано
4
Bioelectrochemistry, Год журнала: 2024, Номер 161, С. 108847 - 108847
Опубликована: Ноя. 15, 2024
Язык: Английский
Процитировано
4
Annals of Medicine, Год журнала: 2025, Номер 57(1)
Опубликована: Янв. 2, 2025
Cerebral amyloid angiopathy (CAA), characterized by the deposition of amyloid-β (Aβ) peptides in walls medium and small vessels brain leptomeninges, is a major cause lobar hemorrhage elderly individuals. Among genetic risk factors for CAA that continue to be recognized, apolipoprotein E (APOE) gene most significant prevalent, as its variants have been implicated more than half all patients with CAA. While presence APOE ε4 allele markedly increases CAA, ε2 confers protective effect relative common ε3 allele. These allelic encode three isoforms differ at two amino acid positions. The primary physiological role mediate lipid transport periphery; however, it has also shown involved wide array biological functions, particularly those involving Aβ, which plays known processing, production, aggregation, clearance. challenges posed reliance on postmortem histological analyses current absence an effective intervention underscore urgency innovative APOE-targeted strategies diagnosing This review not only deepens our understanding impact pathogenesis but can help guide exploration targeted therapies, inspiring further research into therapeutic potential APOE.
Язык: Английский
Процитировано
0
International Journal of Geriatric Psychiatry, Год журнала: 2025, Номер 40(1)
Опубликована: Янв. 1, 2025
ABSTRACT Background Apolipoprotein E (ApoE) ε4 genotype is a well‐known risk factor for Alzheimer's disease (AD). However, its effect on predicting cognitive decline in individuals without dementia and association with age are unclear. Objective To investigate the relationship between ApoE polymorphism of incidence elderly dementia. Methods This population‐based prospective study was conducted 2011 2016. The involved 767 dementia‐free who had undergone analysis, were aged ≥ 60 years, lived rural China. Participants divided into three groups: E3 (genotype 3/3), E4 (genotypes 3/4 4/4), E2 2/3) groups. Results After 5 666 (86.8%) followed up. rate change MMSE score faster group than groups (5.0 ± 4.4 vs. 3.5 3.8 3.9 3.9, p = 0.001), after adjusting age, sex, educational level baseline scores, especially 70–79 years group. In same group, higher (OR 2.850; 95% CI: 1.146–7.090). hypertensive status, level, marital engagement social activities, past history stroke, allele remained an independent 3.070; 1.162–8.110) follow‐up. Conclusions carriers decline. extremely old individuals.
Язык: Английский
Процитировано
0
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0
Redox Biology, Год журнала: 2025, Номер 81, С. 103535 - 103535
Опубликована: Фев. 7, 2025
Conventional pharmacotherapy exhibits limited efficacy in halting cartilage degeneration, whereas exercise interventions have demonstrated promising protective effects against osteoarthritis (OA), albeit with unclear underlying mechanisms. This study investigated the beneficial of swimming mitigating local joint damage through enhancement systemic antioxidant capacity. We found that overexpression superoxide dismutase 3 (SOD3) could promote elimination extracellular reactive oxygen species (ROS) and preserve matrix (C-ECM). Conversely, genetic deletion SOD3 accelerated loss C-ECM contributed to OA due an imbalance oxidative stress. Further investigation revealed interact CCAAT/enhancer binding protein β (C/EBPβ), leading inhibition apolipoprotein E (APOE) transcription subsequent APOE-induced cholesterol transport. Ultimately, we developed targeted vesicles (EVs) high affinity for efficient precise delivery SOD3. Overall, this elucidated potential degenerative disorders SOD3-mediated antioxidation redistribution.
Язык: Английский
Процитировано
0