The Role of Glymphatic System in Alzheimer’s and Parkinson’s Disease Pathogenesis

Biomedicines, Journal Year: 2022, Volume and Issue: 10(9), P. 2261 - 2261

Published: Sept. 13, 2022

Alzheimer's disease (AD) is the most common cause of neurodegenerative dementia, whilst Parkinson's (PD) a movement disorder. These two disorders share accumulation toxic proteins as pathological hallmark. The lack definitive disease-modifying treatments for these neurogenerative diseases has led to hypothesis new pathogenic mechanisms target and design potential therapeutic approaches. recent observation that glymphatic system supposed be responsible cerebrospinal fluid into brain clearance metabolic waste study its involvement in pathogenesis classic proteinopathies. Aquaporin-4 (AQP4), water channel located endfeet astrocyte membrane, considered primary driver system, defective AQP4-mediated drainage been linked objective present review body knowledge links AD PD other lifestyle factors such sleep deprivation exercise may influence function. We will also focus on neuroimaging approaches could identify marker detect changes.

Language: Английский

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Altered Brain Glymphatic Flow at Diffusion-Tensor MRI in Rapid Eye Movement Sleep Behavior Disorder

Radiology, Journal Year: 2023, Volume and Issue: 307(5)

Published: May 9, 2023

Background Brain glymphatic dysfunction may contribute to the development of α-synucleinopathies. Yet, noninvasive imaging and quantification remain lacking. Purpose To examine function brain in isolated rapid eye movement sleep behavior disorder (RBD) its relevance phenoconversion with use diffusion-tensor (DTI) analysis along perivascular space (ALPS). Materials Methods This prospective study included consecutive participants diagnosed RBD, age- sex-matched control participants, Parkinson disease (PD) who were enrolled examined between May 2017 April 2020. All underwent 3.0-T MRI including DTI, susceptibility-weighted susceptibility map–weighted imaging, and/or dopamine transporter using iodine 123–2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane SPECT at time participation. Phenoconversion status α-synucleinopathies was unknown MRI. Participants regularly followed up monitored for any signs The ALPS index reflecting activity calculated by a ratio diffusivities x-axis projection association neural fibers perpendicular them compared according groups Kruskal-Wallis Mann-Whitney U tests. risk RBD evaluated Cox proportional hazards model. Results Twenty (12 men; median age, 73 years [IQR, 66–76 years]), 20 PD included. lower group versus controls (1.53 vs 1.72; P = .001) but showed no evidence difference (1.49; .68). conversion decreased an increasing (hazard ratio, 0.57 per 0.1 increase [95% CI: 0.35, 0.93]; .03). Conclusion DTI-ALPS demonstrated more severe reduction individuals © RSNA, 2023 Supplemental material is available this article. See also editorial Filippi Balestrino issue.

Language: Английский

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Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS): Revisiting the Meaning and Significance of the Method

Magnetic Resonance in Medical Sciences, Journal Year: 2024, Volume and Issue: 23(3), P. 268 - 290

Published: Jan. 1, 2024

More than 5 years have passed since the Diffusion Tensor Image Analysis ALong Perivascular Space (DTI-ALPS) method was proposed with intention of evaluating glymphatic system. This is handy due to its noninvasiveness, provision a simple index in straightforward formula, and possibility retrospective analysis. Therefore, ALPS adopted evaluate system for many disorders studies. The purpose this review look back discuss at moment.

Language: Английский

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Matrix metalloproteinase-9 inhibition prevents aquaporin-4 depolarization-mediated glymphatic dysfunction in Parkinson’s disease

Journal of Advanced Research, Journal Year: 2023, Volume and Issue: 56, P. 125 - 136

Published: March 20, 2023

The glymphatic system offers a perivascular pathway for the clearance of pathological proteins and metabolites to optimize neurological functions. Glymphatic dysfunction plays pathogenic role in Parkinson's disease (PD); however, molecular mechanism PD remains elusive. To explore whether matrix metalloproteinase-9 (MMP-9)-mediated β-dystroglycan (β-DG) cleavage is involved regulation aquaporin-4 (AQP4) polarity-mediated PD. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced A53T mice were used this study. function was evaluated using ex vivo imaging. TGN-020, an AQP4 antagonist, administered investigate GM6001, MMP-9 MMP-9/β-DG regulating AQP4. expression distribution AQP4, MMP-9, β-DG assessed western blotting, immunofluorescence, co-immunoprecipitation. ultrastructure basement membrane (BM)-astrocyte endfeet detected transmission electron microscopy. Rotarod open-field tests performed evaluate motor behavior. Perivascular influx efflux cerebral spinal fluid tracers reduced MPTP-induced with impaired polarization. inhibition aggravated reactive astrogliosis, drainage restriction, dopaminergic neuronal loss mice. cleaved upregulated both mice, polarized localization astrocyte endfeet. restored BM-astrocyte endfeet-AQP4 integrity attenuated metabolic perturbations loss. depolarization contributes aggravates pathologies, MMP-9-mediated regulates through polarization PD, which may provide novel insights into pathogenesis

Language: Английский

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Neuroimaging uncovers distinct relationships of glymphatic dysfunction and motor symptoms in Parkinson’s disease

Journal of Neurology, Journal Year: 2023, Volume and Issue: 270(5), P. 2649 - 2658

Published: March 1, 2023

Language: Английский

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Aquaporin-4 in glymphatic system, and its implication for central nervous system disorders

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 179, P. 106035 - 106035

Published: Feb. 15, 2023

The clearance function is essential for maintaining brain tissue homeostasis, and the glymphatic system main pathway removing interstitial solutes. Aquaporin-4 (AQP4) most abundantly expressed aquaporin in central nervous (CNS) an integral component of system. In recent years, many studies have shown that AQP4 affects morbidity recovery process CNS disorders through system, shows notable variability part pathogenesis these diseases. Therefore, there has been considerable interest as a potential promising target regulating improving neurological impairment. This review aims to summarize pathophysiological role plays several by affecting findings can contribute better understanding self-regulatory functions were involved provide new therapeutic alternatives incurable debilitating neurodegenerative future.

Language: Английский

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Glymphatic system dysfunction predicts amyloid deposition, neurodegeneration, and clinical progression in Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(5), P. 3251 - 3269

Published: March 19, 2024

Abstract INTRODUCTION Although glymphatic function is involved in Alzheimer's disease (AD), its potential for predicting the pathological and clinical progression of AD sequential association with core biomarkers poorly understood. METHODS Whole‐brain activity was measured by diffusion tensor image analysis along perivascular space (DTI‐ALPS) participants dementia ( n = 47), mild cognitive impairment (MCI; 137), normal controls 235) from Disease Neuroimaging Initiative. RESULTS ALPS index significantly lower than MCI or controls. Lower associated faster changes amyloid positron emission tomography (PET) burden signature region interest volume, higher risk amyloid‐positive transition progression, rates amyloid‐ neurodegeneration‐related decline. Furthermore, associations decline were fully mediated PET brain atrophy. DISCUSSION Glymphatic failure may precede pathology, predicts deposition, neurodegeneration, AD. Highlights The (ALPS) reduced patients (AD) dementia, prodromal AD, preclinical predicted accelerated beta (Aβ) Aβ‐positive transition. decrease occurs before cerebrospinal fluid Aβ42 reaches positive threshold. atrophy, Aβ atrophy link

Language: Английский

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The relationship between amyloid pathology, cerebral small vessel disease, glymphatic dysfunction, and cognition: a study based on Alzheimer’s disease continuum participants

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: Feb. 20, 2024

Abstract Background Glymphatic dysfunction is a crucial pathway for dementia. Alzheimer’s disease (AD) pathologies co-existing with cerebral small vessel (CSVD) the most common pathogenesis We hypothesize that AD and CSVD could be associated glymphatic dysfunction, contributing to cognitive impairment. Method Participants completed amyloid PET, diffusion tensor imaging (DTI), T2 fluid-attenuated inversion-recovery (FLAIR) sequences were included from Disease Neuroimaging Initiative (ADNI). White matter hyperintensities (WMH), marker, was evaluated T2FLAIR images represented burden of CSVD. Amyloid PET used assess Aβ aggregation in brain. image analysis along perivascular space (DTI-ALPS) index, enlarged spaces (PVS), choroid plexus volume reflect function. The relationships between WMH burden/Aβ these markers as well correlations function investigated. Furthermore, we conducted mediation analyses explore potential mediating effects relationship cognition. Results One hundred thirty-three participants continuum included, consisting 40 CN − , 48 + 26 MCI 19 participants. Our findings revealed there negative associations whole-brain ( r = 0.249, p 0.022) 0.458, < 0.001) DTI-ALPS. Additionally, 0.223, 0.041) 0.294, 0.006) both positively volume. However, did not observe significant PVS enlargement severity. DTI-ALPS memory 0.470, FDR- 0.001), executive 0.358, visual-spatial 0.040), language 0.419, 0.001). Conversely, showed 0.315, 0.007), 0.321, 0.233, 0.031), 0.261, 0.021). There no severity performance. In analysis, found acted mediator accumulation performances. Conclusion study provided evidence pathology (Aβ) which further related These results may provide theoretical basis new targets treating AD.

Language: Английский

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Sleep disorders cause Parkinson's disease or the reverse is true: Good GABA good night

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(3)

Published: March 1, 2024

Parkinson's disease (PD) is a progressive neurodegenerative brain due to degeneration of dopaminergic neurons (DNs) presented with motor and non-motor symptoms. PD symptoms are developed in response the disturbance diverse neurotransmitters including γ-aminobutyric acid (GABA). GABA has neuroprotective effect against neuropathology by protecting DNs substantia nigra pars compacta (SNpc). It been shown that GABAergic linked progression neurotransmission necessary pathway for normal sleep patterns, thus deregulation could be potential cause disorders PD.

Language: Английский

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The relationship between inflammation, impaired glymphatic system, and neurodegenerative disorders: A vicious cycle

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 192, P. 106426 - 106426

Published: Feb. 6, 2024

The term "glymphatic" emerged roughly a decade ago, marking pivotal point in neuroscience research. glymphatic system, glial-dependent perivascular network distributed throughout the brain, has since become focal of investigation. There is increasing evidence suggesting that impairment system appears to be common feature neurodegenerative disorders, and this exacerbates as disease progression. Nevertheless, factors contributing dysfunction across most disorders remain unclear. Inflammation, however, suspected play role. Dysfunction can lead significant accumulation protein waste products, which trigger inflammation. interaction between inflammation cyclical potentially synergistic. Yet, current research limited, there lack comprehensive models explaining association. In perspective review, we propose novel model inflammation, impaired function, interconnected vicious cycle. By presenting experimental from existing literature, aim demonstrate that: (1) aggravates dysfunction, (2) exacerbated progression, (3) progression promotes Finally, implication proposed discussed.

Language: Английский

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