Published: Jan. 1, 2025
Language: Английский
GeroScience, Journal Year: 2024, Volume and Issue: unknown
Published: June 3, 2024
Abstract Aging plays a pivotal role in the pathogenesis of cerebral small vessel disease (CSVD), contributing to onset and progression vascular cognitive impairment dementia (VCID). In older adults, CSVD often leads significant pathological outcomes, including blood–brain barrier (BBB) disruption, which turn triggers neuroinflammation white matter damage. This damage is frequently observed as hyperintensities (WMHs) neuroimaging studies. There mounting evidence that adults with atherosclerotic diseases, such peripheral artery disease, ischemic heart carotid stenosis, face heightened risk developing VCID. review explores complex relationship between atherosclerosis, CSVD, BBB disruption. It continuum aging, emphasizing shared pathomechanisms underlie atherosclerosis large arteries disruption microcirculation, exacerbating both By reviewing current evidence, this paper discusses impact endothelial dysfunction, cellular senescence, inflammation, oxidative stress on neurovascular health. aims enhance understanding these interactions advocate for integrated approaches manage health, thereby mitigating
Language: Английский
Citations
23
European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)
Published: June 8, 2024
The brain-bone axis has emerged as a captivating field of research, unveiling the intricate bidirectional communication between central nervous system (CNS) and skeletal metabolism. This comprehensive review delves into current state knowledge surrounding axis, exploring complex mechanisms, key players, potential clinical implications this fascinating area study. discusses neural regulation bone metabolism, highlighting roles sympathetic system, hypothalamic neuropeptides, neurotransmitters in modulating remodeling. In addition, it examines influence bone-derived factors, such osteocalcin fibroblast growth factor 23, on brain function behavior. therapeutic targeting context neurological disorders is also explored. By unraveling interplay CNS aims to provide resource for researchers, clinicians, students interested its human health disease.
Language: Английский
Citations
18
Cerebral Circulation - Cognition and Behavior, Journal Year: 2024, Volume and Issue: 6, P. 100216 - 100216
Published: Jan. 1, 2024
The disruption of the neurovascular unit (NVU), which maintains integrity blood brain barrier (BBB), has been identified as a critical mechanism in development cerebrovascular and neurodegenerative disorders. However, understanding pathophysiological mechanisms linking NVU dysfunction to disorders is incomplete, reliable biomarkers measure are yet be established. This systematic review meta-analysis aimed identify associated with BBB large vessel disease, small disease (SVD) vascular cognitive (VCD). A literature search was conducted PubMed, EMBASE, Scopus PsychINFO related pathologies published until 20 November 2023. Studies that assayed one or more specific markers human serum plasma were included. Quality studies assessed using Newcastle-Ottawa Assessment Scale. Effects pooled methodological heterogeneity examined random effects model. total 117 included this review. Where study numbers allowed, analysed effect for VCD (1 biomarker; 5 studies) disorders, including stroke SVD (9 biomarkers; 27 while all remaining (n=17 77 through qualitative analysis. Results revealed cerebrospinal fluid/serum albumin quotient (Q-Alb) reliably differentiates patients from healthy controls (MD = 2.77; 95% CI 1.97 3.57; p <0.0001) commonly measured endothelial (VEGF, VCAM-1, ICAM-1, vWF E-selectin) neuronal injury (NfL) significantly elevated pathologies. assessment non-meta-analysed NSE, NfL, vWF, lipocalin-2, MMP-2 MMP-9 levels upregulated VCD, although these findings not consistently replicated. identifies several promising require further validation. panel representing multiple pathways may offer greater discriminative power distinguishing possible VCD.
Language: Английский
Citations
16
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4401 - 4401
Published: April 16, 2024
The circadian rhythms generated by the master biological clock located in brain's hypothalamus influence central physiological processes. At molecular level, a core set of genes interact to form transcription-translation feedback loops that provide basis rhythm. In animal models disease, desynchronization peripheral tissues with has been detected. Interestingly, patients vascular dementia have sleep disorders and irregular patterns. These alterations impact hormonal levels, cardiovascular health (including blood pressure regulation vessel function), pattern expression activity antioxidant enzymes. Additionally, oxidative stress can arise from ischemia-reperfusion injury, amyloid-beta production, abnormal phosphorylation tau protein, neurotransmitters, among others. Several signaling pathways are involved pathogenesis dementia. While precise mechanisms linking still being studied, there is evidence suggest maintaining healthy patterns supporting proper rhythm function may be important for reducing risk Here, we reviewed main action targets related cycle
Language: Английский
Citations
9
Nature Reviews Bioengineering, Journal Year: 2024, Volume and Issue: 2(8), P. 691 - 709
Published: June 5, 2024
Language: Английский
Citations
8
Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 14, 2025
Abstract INTRODUCTION Using an Asian cohort with high prevalence of concomitant cerebrovascular disease (CeVD), we evaluated the performance a plasma immunoassay for tau phosphorylated at threonine 217 (p‐tau217) in detecting amyloid beta positivity (Aβ+) on positron emission tomography and cognitive decline, based three‐range reference, which stratified patients into low‐, intermediate‐, high‐risk groups Aβ+. METHODS Brain status (Aβ– [ n = 142] vs Aβ+ 73]) PET scans was assessed along ALZpath p‐tau217 assay to derive reference points 90% sensitivity (lower threshold) specificity (upper threshold). RESULTS Plasma (area under curve [AUC] 0.923) outperformed routine clinical assessments (AUC 0.760–0.819; p ≤ 0.003) other biomarkers 0.817–0.834; < 0.001). The group showed significantly higher rates decline than low‐risk group. DISCUSSION Risk stratification demonstrated potential diagnostic prognostic utility CeVD. Highlights detect brain pathology studied superior compared neuroimaging measures, workup, or blood including p‐tau181, glial fibrillary protein (GFAP), Aβ Higher correlated faster shows promise as Alzheimer's (AD) biomarker diverse populations
Language: Английский
Citations
1
Stroke, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 17, 2025
Endothelial dysfunction and inflammation have been implicated in the pathophysiology of cerebral small vessel disease (SVD). However, whether they are causal, if so which components pathways represent potential treatment targets, remains uncertain. Two-sample Mendelian randomization (MR) was used to test association between circulating abundance 996 proteins involved endothelial SVD. The genetic instruments predicting protein levels were obtained from Iceland 36K (n=35 892) UK Biobank Proteomics (n=34 557) cohorts, both longitudinal studies with follow-up 2000 2023 2006 2023, respectively. SVD represented by lacunar stroke (n=6030 cases) 5 neuroimaging features (white matter hyperintensities [n=55 291], diffusion tensor imaging metrics: mean diffusivity [n=36 460] fractional anisotropy 533], extensive white perivascular space burden [n=9324 cases], microbleeds [n=3556 cases]). Among supported causal evidence MR, cross-sectional analysis performed assess their associations cognitive performance; survival Fine-Gray models applied examine incident all-cause dementia within cohort. MR suggested COL2A1 (collagen type II α-1 chain) associated (odds ratio, 0.89 [95% CI, 0.86-0.91]; P=5×10-5). Moreover, 12 related function Cross-sectional analyses showed 13 (EPHA2 [ephrin type-A receptor 2], METAP1D [methionine aminopeptidase 1D, mitochondrial], FLT4 [vascular growth factor 3], COL2A1, TIMD4 [T-cell immunoglobulin mucin domain-containing 4]) performance effects concordant findings. Survival indicated that (EPHA2, METAP1D, FLT4, APOE [apolipoprotein E], PDE5A [cGMP-specific 3',5'-cyclic phosphodiesterase]) risk or independent age sex, consistent evidence. Our findings suggest endothelial-platelet activation complement-mediated regulation play roles identify therapeutic targets pathways.
Language: Английский
Citations
1
Current Opinion in Psychiatry, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 22, 2025
Purpose of review Recent advancements in molecular biomarkers and therapeutic options for Alzheimer's disease have brought into focus the need greater progress second most common cause dementia, vascular cognitive impairment dementia (VCID). We examine how study monogenic causes VCID has contributed to understanding its pathophysiology potential biomarker treatment research. findings It is widely accepted that conditions which disrupt cerebral small vessels contribute pathologies including stroke microbleeds, ultimately leading dementia. Among these are a range vessel diseases (SVDs) such as CADASIL, CARASIL, Fabry COL4A-related disorders. Summary This indicates importance furthering research SVDs order gain insight pathomechanisms more broadly. Monogenic easier model than sporadic can serve guide identifying diagnosis, monitoring intervention outcomes.
Language: Английский
Citations
1
Brain, Journal Year: 2024, Volume and Issue: 147(10), P. 3286 - 3305
Published: June 25, 2024
Cell-based therapies hold great promise for brain repair after stroke. While accumulating evidence confirms the preclinical and clinical benefits of cell therapies, underlying mechanisms by which they promote remain unclear. Here, we briefly review endogenous ischaemic stroke then focus on how different stem progenitor sources can repair. Specifically, examine transplanted grafts contribute to improved functional recovery either through direct replacement or stimulating pathways. Additionally, discuss recently implemented refinement methods, such as preconditioning, microcarriers, genetic safety switches universal (immune evasive) transplants, well therapeutic potential these pharmacologic manipulations further enhance efficacy therapies. By gaining a deeper understanding post-ischaemic mechanisms, prospective trials may be refined advance post-stroke therapy clinic.
Language: Английский
Citations
6
Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16
Published: Feb. 8, 2024
Vascular dementia (VD) is a prevalent cognitive disorder among the elderly. Its pathological mechanism encompasses neuronal damage, synaptic dysfunction, vascular abnormalities, neuroinflammation, and oxidative stress, others. In recent years, extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have garnered significant attention as an emerging therapeutic strategy. Current research indicates that MSC-derived (MSC-EVs) play pivotal role in both diagnosis treatment of VD. Thus, this article delves into advancements MSC-EVs VD, discussing mechanisms by which EVs influence pathophysiological processes These form theoretical foundation for their neuroprotective effect VD treatment. Additionally, highlights potential applications diagnosis. conclusion, present promising innovative strategy With rigorous ongoing innovation, concept can transition practical clinical treatment, providing more effective options patients.
Language: Английский
Citations
5