The role and mechanism of Aβ clearance dysfunction in the glymphatic system in Alzheimer’s disease comorbidity DOI Creative Commons

H L Li,

Qianqian Yao, Xueyan Huang

et al.

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 25, 2024

Alzheimer’s disease (AD) is the leading type of dementia globally, characterized by a complex pathogenesis that involves various comorbidities. An imbalance in production and clearance amyloid β-protein (Aβ) peptides brain key pathological mechanism AD, with glymphatic system playing crucial role Aβ clearance. Comorbidities associated such as diabetes, depression, hypertension, not only affect but also impair brain’s lymphatic system. Abnormalities structure function this further weaken capabilities, presence comorbidities may exacerbate process. This paper aims to review specific mechanisms impaired via context AD comorbidities, providing new insights for prevention treatment AD. Overall, damage primarily focuses on aquaporin-4 (AQP4) perivascular spaces (PVS), suggesting maintaining health help slow progression its Additionally, given ongoing controversies regarding system, revisits discusses principles characteristics current detection methods

Language: Английский

Glymphatic function decline as a mediator of core memory-related brain structures atrophy in aging DOI

Shan Chong,

Sanwang Wang, Teng Gao

et al.

Journal of Translational Internal Medicine, Journal Year: 2025, Volume and Issue: 13(1), P. 65 - 77

Published: Feb. 1, 2025

This study aimed to elucidate the role of glymphatic system-a crucial pathway for clearing waste in brain-in aging process and its contribution cognitive decline. We specifically focused on diffusion tensor imaging analysis along perivascular space (ALPS) index as a noninvasive biomarker function. Data were drawn from Alzheimers Disease Neuroimaging Initiative (ADNI) database separate validation cohort analyze ALPS cognitively normal older adults. The relationships among index, brain morphometry, memory performance examined. As function, appeared decline with age both cohorts. According morphology analysis, was positively correlated thickness left entorhinal cortex (r = 0.258, P false discovery rate (FDR) 2.96 × 10-4), it played mediating between thinning. independent further validated correlation 0.414, FDR 0.042). Additionally, primary cohorts, significant relationship durable or delayed highlights promising function links atrophy core regions during aging. Furthermore, these results suggest that targeting dysfunction could represent novel therapeutic approach mitigate age-related

Language: Английский

Citations

0
Cerebrovascular burden and neurodegeneration linked to 15-year odor identification decline in older adults DOI Creative Commons
Javier Oltra, Grégoria Kalpouzos, Ingrid Ekström

et al.

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

Published: March 24, 2025

Background The mechanisms underlying olfactory decline in aging need further investigation. Noticeably, the longitudinal relationship of biological markers with olfaction remains underexplored. We investigated whether baseline levels and progression microvascular lesions brain atrophy are associated odor identification (OID) decline. Methods association between structural MRI OID was examined participants from SNAC-K study who were free dementia at ( n = 401, mean age 70.2 years, 60% females). repeatedly assessed over 15 years. Presence lacunes, white matter hyperintensities (WMH), perivascular spaces (PVS), lateral ventricular, hippocampal, amygdalar, total gray (GM) volumes up to 6 concurrent first years assessments. Results Higher PVS count lower hippocampal GM accelerated p FWE < 0.05). Longitudinally 225), presence lacunes follow-up, faster WMH volume increases, ventricular enlargement, Conclusion Olfactory is related both increased cerebrovascular burden time.

Language: Английский

Citations

0
Mechanistic insights into the sleep-glymphopathy-cerebral small vessel disease loop: implications for epilepsy pathophysiology and therapy DOI Creative Commons
Zaw Myo Hein,

Zaid Adnan Subhi Al-Zaghal,

Mazira Mohamad Ghazali

et al.

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: March 27, 2025

Epilepsy is the second most common neurological disorder and affects approximately 50 million people worldwide. Despite advances in antiepileptic therapy, about 30% of patients develop refractory epilepsy. Recent studies have shown sleep, glymphatic function, cerebral small vessel disease (CSVD), epilepsy are interrelated by sharing a multidirectional relationship influencing their severity progression. Sleep plays vital role brain homeostasis promotes clearance responsible for removal metabolic wastes neurotoxic substances from brain. Disrupted sleep feature can lead to impairment efficiency or glymphopathy, promoting neuroinflammation accrual epileptogenic factors. CSVD, occurring up 60% aging population, further exacerbates neurovascular compromise neurodegeneration increasing seizure susceptibility worsening outcomes. This narrative review aims discuss molecular pathophysiological inter-relationships between these factors, providing new framework that places glymphopathy CSVD as contributors epileptogenesis conditions disruption. We propose an integrative model wherein vascular insufficiency interact positive feedback loop disruption increased vulnerability mediated epileptic activity. Acknowledging interactions has significant impacts on both research clinical practice. Targeting modulation, cerebrovascular health presents promising avenue therapeutic intervention. Future should focus developing precision medicine approaches integrate neuro-glial-vascular mechanisms optimize management. Clinically, addressing disturbances may improve treatment effectiveness, reduce burden, overall highlights need interdisciplinary break vicious cycle epilepsy, disturbance, pathology, paving way innovative paradigms.

Language: Английский

Citations

0
The glymphatic system in Huntington's disease DOI Creative Commons
Wenzhen Duan,

Zhou Yuan,

Hongshuai Liu

et al.

Journal of Huntington s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

The glymphatic system, a macroscopic waste clearance network in the brain, plays vital role maintaining neuronal health and brain homeostasis. Functionally analogous to lymphatic system other organs, term “glymphatic” combines “glial” “lymphatic.” This facilitates exchange of cerebrospinal fluid (CSF) interstitial (ISF) parenchyma, aiding removal soluble proteins metabolites while distributing essential nutrients signaling molecules. Its functionality is closely tied aquaporin 4 (AQP4) water channels, located primarily on astrocytic endfeet, which mediate movement between CSF ISF. Proper function relies cellular distribution AQP4 channels its astroglial endfeet polarization. Emerging evidence links dysfunction several neurodegenerative disorders, including Huntington's disease (HD). Understanding HD pathogenesis could provide novel insights into new therapeutic approaches. review examines connection HD, highlighting future research directions advancement for HD. It explores pharmacological interventions lifestyle modifications aimed at optimizing improve management.

Language: Английский

Citations

0
Diffusion along Perivascular Spaces as a Marker for Glymphatic System Impairment in Huntington's Disease DOI Creative Commons

Jin‐Hui Yin,

LingXiao Cao, Yang Liu

et al.

Movement Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Abstract Background The aim was to investigate if glymphatic function is impaired in patients with Huntington's disease (HD) and its clinical relevance. Methods Forty‐nine subjects carrying mutant Huntingtin (m HTT ), comprising 35 manifest (mHD) 14 pre‐manifest (PreHD), healthy controls (HC) were recruited this study. diffusion along perivascular spaces (ALPS) index the percentage of space basal ganglia (pPVS_BG) obtained different groups. discrimination effects ALPS detected using receiver operating characteristic (ROC) analysis, correlations features HD further analyzed. Results decreased m carriers compared HCs, it lower mHD PreHD patients. ROC analysis showed that could discriminate from HC (AUC [area under curve] = 0.903), 0.886), 0.755). Lower correlated greater burden, severity disease, lager pPVS_BG, brain volume thickness cortices. Regression predict performance motor cognitive functions. Mediation revealed partially mediated CAG repeat age on decline HD. Conclusions This study demonstrated impairment system, especially paraventricular white matter BG, manifestations, structural changes carriers. © 2025 Author(s). Movement Disorders published by Wiley Periodicals LLC behalf International Parkinson Disorder Society.

Language: Английский

Citations

0
Glymphatic Pathway Dysfunction in Severe Obstructive Sleep Apnea: A Meta-Analysis DOI
Sadegh Ghaderi, Sana Mohammadi, Farzad Fatehi

et al.

Sleep Medicine, Journal Year: 2025, Volume and Issue: 131, P. 106528 - 106528

Published: April 21, 2025

Language: Английский

Citations

0
Glymphatic System Assessment Using Diffusion Tensor Images: Introducing the New-ALPS Index Through Genetic Programming DOI
Mahmood Amiri,

Ahmadali Jamali,

Majid Abbasi Sisara

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Abstract The glymphatic system is essential for the clearance of waste products from brain, and its dysfunction associated with cognitive decline in neurodegenerative diseases such as Alzheimer's Disease (AD) Mild Cognitive Impairment (MCI). In literature, along perivascular space (ALPS) index was employed to assess activity human using diffusion tensor images (DTI). this research, a new ALPS (called New-ALPS), introduced which fact optimized version through Genetic Programming. New-ALPS left right hemispheres are calculated separately. For whole brain two ways presented: taking average values hemisphere called New-ALPS(avg) or their sum, New-ALPS(sum). comparison classic index, exhibits stronger correlation measures, including Mini-Mental State Examination (MMSE) (2.78% improvement), Clinical Dementia Rating (CDR) (5.13% Functional Activities Questionnaire (FAQ) (10% demonstrated by analysis fiber diffusivities DTI data Neuroimaging Initiative (ADNI) dataset. Furthermore, enhanced sensitivity identifying effects aging (5.78 times improvement AD individuals, negative 3 MCI 12.42 normal controls) sleep disorders (28.57% MMSE, 11.11% Pittsburgh Sleep Quality Index (PSQI) Human Connectome Project (HCP) Our results indicate that may be more reliable metric evaluating system, providing novel insights into pathophysiology diseases.

Language: Английский

Citations

0
The role and mechanism of Aβ clearance dysfunction in the glymphatic system in Alzheimer’s disease comorbidity DOI Creative Commons

H L Li,

Qianqian Yao, Xueyan Huang

et al.

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 25, 2024

Alzheimer’s disease (AD) is the leading type of dementia globally, characterized by a complex pathogenesis that involves various comorbidities. An imbalance in production and clearance amyloid β-protein (Aβ) peptides brain key pathological mechanism AD, with glymphatic system playing crucial role Aβ clearance. Comorbidities associated such as diabetes, depression, hypertension, not only affect but also impair brain’s lymphatic system. Abnormalities structure function this further weaken capabilities, presence comorbidities may exacerbate process. This paper aims to review specific mechanisms impaired via context AD comorbidities, providing new insights for prevention treatment AD. Overall, damage primarily focuses on aquaporin-4 (AQP4) perivascular spaces (PVS), suggesting maintaining health help slow progression its Additionally, given ongoing controversies regarding system, revisits discusses principles characteristics current detection methods

Language: Английский

Citations

1