Shared Mechanisms of Blood-Brain Barrier Dysfunction and Neuroinflammation in COVID-19 and Alzheimer’s Disease DOI Creative Commons
Meredith G. Mayer, Tracy Fischer

American Journal Of Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

The COVID-19 pandemic, caused by SARS-CoV-2, has highlighted the virus's impact on central nervous system (CNS) and its potential to exacerbate neurodegenerative diseases like Alzheimer's disease (AD). Emerging evidence suggests that SARS-CoV-2 infection contributes chronic neuroinflammation, a key driver in etiopathogenesis of AD. Shared mechanisms, including blood-brain barrier (BBB) dysfunction, systemic inflammation, activation immune pathways, may link AD onset and/or progression, particularly among vulnerable individuals, such as those advanced age. This review explores convergent pathways involving renin-angiotensin-aldosterone (RAAS), Wnt/β-catenin signaling, NFκB activation, interferon (IFN) focusing their roles BBB integrity neuroinflammation. SARS-CoV-2-mediated ACE2 depletion disrupts RAAS homeostasis, favoring proinflammatory signaling parallels vascular dysfunction Dysregulation exacerbates permeability, while IFN contribute breakdown propagate CNS inflammation via endothelial cell activation. These interactions amplify prodromal pathology initiate pathogenesis. By identifying mechanistic overlaps between AD, this underscores need for therapeutic strategies targeting shared dysfunction. Understanding these connections is critical mitigating long-term neurological sequelae reducing burden

Language: Английский

Chronic Postsurgical Pain Raises Risk of Dementia DOI Open Access
Mingyang Sun, Xiaolin Wang, Zhongyuan Lu

et al.

European Journal of Pain, Journal Year: 2025, Volume and Issue: 29(4)

Published: Feb. 21, 2025

ABSTRACT Purpose This study aimed to investigate the association between chronic postsurgical pain (CPSP) and risk of dementia, addressing a significant gap in existing literature highlighting potential implications for clinical practice public health. Patients Methods Utilising data from Taiwan's National Health Insurance Research Database, propensity score‐matched cohort was conducted involving 142,682 patients who underwent major surgery 2004 2018. CPSP defined as prolonged analgesic use post‐surgery, dementia diagnosis tracked until December 31, 2022. Multivariable Cox regression models were employed calculate adjusted hazard ratios (aHRs) versus non‐CPSP groups. Results Before score matching, ( n = 37,438) exhibited higher with aHRs 1.35 (95% CI: 1.30–1.40). After aHR remained elevated at 1.31 1.26–1.37), indicating risk. Subgroup analysis confirmed this across various demographic factors, sensitivity reinforcing robustness findings. Conclusion establishes an independent predictor risk, importance postoperative management mitigating long‐term cognitive outcomes. Approximately 30% post‐CPSP presents opportunity reduction through effective strategies, emphasising need targeted interventions address critical healthcare issue. Significance provides compelling evidence that significantly increases previously underexplored connection decline. By establishing our findings underscore strategies surgical patients, particularly mitigate heightened improve

Language: Английский

Citations

1

Sleep disturbance and cognition in the elderly: a narrative review DOI Creative Commons
Yuanbo Ni, Min Yu, Cunming Liu

et al.

Anesthesiology and Perioperative Science, Journal Year: 2024, Volume and Issue: 2(3)

Published: Aug. 5, 2024

Abstract Sleep is an essential physiological process that promotes physical recovery and helps consolidate learning memory. Common manifestations of sleep disturbances include insomnia, hypersomnia, circadian rhythm disorders, parasomnias, all which impair cognitive function, particularly in the elderly. Cognitive impairment a significant factor threatens quality life elderly, there currently no effective treatment for conditions such as dementia. The relationship between cognition complex. Studies have shown disorders adversely affect function increase incidence decline. This article focuses on their effects elderly by reviewing research conducted over past 20 years describing potential mechanisms. Additionally, we explore during perioperative period, aiming to identify strategies optimizing quality. We believe this review provides deeper understanding association offers new perspective management.

Language: Английский

Citations

6

Cell-specific transcriptional signatures of vascular cells in Alzheimer’s disease: perspectives, pathways, and therapeutic directions DOI Creative Commons
Soumilee Chaudhuri, Minyoung Cho,

Julia C. Stumpff

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 29, 2025

Abstract Alzheimer’s disease (AD) is a debilitating neurodegenerative that marked by profound neurovascular dysfunction and significant cell-specific alterations in the brain vasculature. Recent advances high throughput single-cell transcriptomics technology have enabled study of human vasculature at an unprecedented depth. Additionally, understudied niche cerebrovascular cells, such as endothelial mural their subtypes been scrutinized for understanding cellular transcriptional heterogeneity AD. Here, we provide overview rich signatures derived from recent single-nucleus transcriptomic studies vascular cells implications targeted therapy We conducted in-depth literature search using Medline Covidence to identify pertinent AD utilized technologies post-mortem tissue focusing on differences cell types cognitively normal older adults. also discuss impaired crosstalk between neuroglial units, well astrocytes contextualize findings distinct smooth muscle fibroblasts, pericytes highlight pathways potential therapeutic interventions concerted multi-omic effort with spatial technology, neuroimaging, neuropathology. Overall, detailed account crucial unit. Graphical Endothelial mediate dysregulated cell-cell interactions The unit (NVU) composed various types, including (pericytes, cells), fibroblast neurons, microglia, astrocytes. Dysregulated involve multiple pathways, notably immune responses, angiogenesis common both cells. involving neuroinflammation amyloid clearance are prominent while exhibit related growth factors, cytoskeletal remodeling synaptic function. In addition, within NVU gliovascular (GVU) altered AD, communication evident, increased pericytes, decreased astrocytes, neurons. Figure created BioRender.com. Abbreviations: Alzheimer's disease; NVU, Neurovascular unit; CNS, Central Nervous System.

Language: Английский

Citations

0

Shared Mechanisms of Blood-Brain Barrier Dysfunction and Neuroinflammation in COVID-19 and Alzheimer’s Disease DOI Creative Commons
Meredith G. Mayer, Tracy Fischer

American Journal Of Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

The COVID-19 pandemic, caused by SARS-CoV-2, has highlighted the virus's impact on central nervous system (CNS) and its potential to exacerbate neurodegenerative diseases like Alzheimer's disease (AD). Emerging evidence suggests that SARS-CoV-2 infection contributes chronic neuroinflammation, a key driver in etiopathogenesis of AD. Shared mechanisms, including blood-brain barrier (BBB) dysfunction, systemic inflammation, activation immune pathways, may link AD onset and/or progression, particularly among vulnerable individuals, such as those advanced age. This review explores convergent pathways involving renin-angiotensin-aldosterone (RAAS), Wnt/β-catenin signaling, NFκB activation, interferon (IFN) focusing their roles BBB integrity neuroinflammation. SARS-CoV-2-mediated ACE2 depletion disrupts RAAS homeostasis, favoring proinflammatory signaling parallels vascular dysfunction Dysregulation exacerbates permeability, while IFN contribute breakdown propagate CNS inflammation via endothelial cell activation. These interactions amplify prodromal pathology initiate pathogenesis. By identifying mechanistic overlaps between AD, this underscores need for therapeutic strategies targeting shared dysfunction. Understanding these connections is critical mitigating long-term neurological sequelae reducing burden

Language: Английский

Citations

0