Morning Blue Light Therapy for TBI, Alzheimer’s, Parkinson’s, and Glymphatic Drainage in ME/CFS and Long Haul. Methylene Blue Implications.
*This article is not medical advice. Before starting on any health related regimen, seek the advice of your Primary Care Physician or an M.D.
Blue Light Therapy
In 2017, an article discussing how morning exposure to blue light (Blue Light Therapy) helps with recovery from traumatic brain injury (TBI) was published. More recently, in 2025 an article came out touting the benefits of morning Blue Light Therapy for Alzheimer’s. I have personal experience with this, as Blue Light Therapy was part of my own healing from two separate brain injuries. Well, it turns out that blue light helps initiate glymphatic drainage. This is important because, in short, the glymphatic drainage system functions to clear metabolic waste from the brain, and dysfunctional glymphatic drainage is a suspected component of Long Haul and ME/CFS and dysregulation of cerebrospinal fluid (CSF).
Aquaporin-4 (AQP4) is a water protein channel in the brain that helps facilitate normal glymphatic drainage. The development of antibodies to AQP4 can be an issue, which is why I test for these antibodies when I suspect a client may have issues with glymphatic drainage. Interestingly, Dr. Steven Gundry, MD espouses that lectins negatively affect Aquaporin-4.
Why Read This Article?
You may be interested in reading this article if:
You want to learn about how Blue Light Therapy can help with TBI recovery.
You want to understand how Blue Light Therapy can help with Alzheimer’s and Parkinson’s.
You want to understand how Blue Light Therapy impacts glymphatic drainage.
You want to learn about Aquaporin-4’s impact on glymphatic drainage.
Highlights From A Study On Blue Light Therapy and TBI
"We observed a significant impact of the blue light treatment (relative to the placebo) on the amount of water diffusion for multiple brain areas, including the corpus callosum, anterior corona radiata, and thalamus. Moreover, many of these changes were associated with improvements in sleep latency and delayed memory. These findings suggest that blue wavelength light exposure may serve as one of the potential non-pharmacological treatments for facilitating structural and functional recovery following mTBI…." [1]
Highlights From A Study On Blue Light Therapy and Alzheimer’s
“Our findings reveal that light treatment prevents memory decline in 4-month-old 5xFAD mice and motivation loss in 14-month-old 5xFAD mice, accompanied by restoration of glial water channel aquaporin-4 polarity, improved brain drainage efficiency, and a reduction in hippocampal lipid accumulation. We further demonstrate the beneficial effects of 40 hertz blue light are mediated through the activation of the vLGN/IGL-Re visual circuit. Notably, concomitant use of anti-Aβ antibody with 40 hertz blue light demonstrates improved soluble Aβ clearance and cognitive performance in 5xFAD mice. These findings offer functional evidence on the therapeutic effects of 40 hertz blue light in Aβ-related pathologies and suggest its potential as a supplementary strategy……Here, the authors show that 40 hertz blue light activates a visual circuit to boost glymphatic drainage, and enhances memory, motivation, and anti-Aβ therapy efficacy in a mouse model of AD…”[2]
40 Hz blue light treatment improves memory functions in 4-month-old 5xFAD mice
Blue light treatment increases glymphatic drainage in 4-month-old 5xFAD mice
AQP4 polarity, glymphatic drainage efficiency, and cognitive functions of 5xFAD mice are improved by 40 Hz blue light through the activation of vLGN/IGL-Re visual circuit
Blockade of brain drainage pathway or AQP4 function prevents the improvement of memory functions in 5xFAD mice by blue light treatment
Blue light treatment decreases lipid accumulation in the hippocampus of 5xFAD mice
Blue light treatment enhances motivative behaviors and glymphatic drainage in 14-month-old 5xFAD mice
Blue light treatment enhances the efficacy of anti-Aβ immunotherapy on cognitive improvement and soluble Aβ reduction
“To summarize, our findings reveal that low-intensity 40 Hz blue light treatment enhances glymphatic drainage and cognitive performance that are functionally associated with the vLGN/IGL-Re circuit and AQP4. The same treatment also improves motivation and glymphatic function in the middle age 5xFAD mice. Furthermore, the combination of anti-Aβ immunotherapy with 40 Hz blue light treatment exhibits increased effects than immunotherapy alone in alleviating cognitive impairment and reducing soluble Aβ42. Collectively, our findings highlight the therapeutic potential and safety of low-intensity 40 Hz blue light treatment and as the adjunctive therapy of anti-Aβ immunotherapy for patients with dementia.”[2]
Glymphatic Drainage and the Role of Aquaporin-4
Glymphatic drainage refers to the removal of metabolic waste products from the brain via the glymphatic system.
Glymphatic System:
The glymphatic system is a brain-wide pathway that supports the exchange of CSF and interstitial fluid (ISF) in the brain. It plays a vital role in removing waste products, such as amyloid-beta, from the brain.
“The glymphatic system is a fluid transport network of cerebrospinal fluid (CSF) entering the brain along arterial perivascular spaces, exchanging with interstitial fluid (ISF), ultimately establishing directional clearance of interstitial solutes. CSF transport is facilitated by the expression of aquaporin-4 (AQP4) water channels on the perivascular end feet of astrocytes. Mice with genetic deletion of AQP4 (AQP4 KO) exhibit abnormalities in the brain structure and molecular water transport.”[4]
Aquaporin-4 (AQP4):
AQP4 is essential for rapid glymphatic transport, particularly in facilitating the movement of water between the perivascular space and the glial tissue. It's also involved in regulating water balance in the brain.
Aquaporin-4 (AQP4) is a crucial protein in the brain's glymphatic system, which is responsible for removing waste products and clearing fluid from the brain. It acts as a water channel, facilitating the exchange of fluid between the brain and the cerebrospinal fluid (CSF). AQP4 is primarily found on the astrocytes in the perivascular spaces, the area around blood vessels in the brain.
“The clearance function is essential for maintaining brain tissue homeostasis, and the glymphatic system is the main pathway for removing brain interstitial solutes. Aquaporin-4 (AQP4) is the most abundantly expressed aquaporin in the central nervous system (CNS) and is an integral component of the glymphatic system. In recent years, many studies have shown that AQP4 affects the morbidity and recovery process of CNS disorders through the glymphatic system, and AQP4 shows notable variability in CNS disorders and is part of the pathogenesis of these diseases. Therefore, there has been considerable interest in AQP4 as a potential and promising target for regulating and improving neurological impairment. This review aims to summarize the pathophysiological role that AQP4 plays in several CNS disorders by affecting the clearance function of the glymphatic system. The findings can contribute to a better understanding of the self-regulatory functions in CNS disorders that AQP4 were involved in and provide new therapeutic alternatives for incurable debilitating neurodegenerative disorders of CNS in the future.”[3]
Location and Importance:
AQP4 is highly concentrated in the perivascular endfeet of astrocytes, where it's critical for maintaining brain homeostasis. It's the most abundant aquaporin in the central nervous system (CNS).
Consequences of APQ4 Dysfunction:
Disrupted AQP4 expression or localization can lead to glymphatic system dysfunction, potentially causing waste product accumulation and contributing to neurodegenerative diseases like Alzheimer's disease.
Implications for Neurodegenerative Diseases:
Studies have shown that AQP4 levels in CSF are higher in individuals with neurodegenerative diseases, suggesting a potential link between AQP4 and the progression of these conditions.
In essence, AQP4 acts as a gatekeeper for water movement in the glymphatic system, playing a crucial role in brain waste clearance and fluid balance. Its dysfunction can have significant implications for brain health and neurodegenerative diseases.
Causes of Blockade of AquaPorin-4 [5]
Aquaporin-4 (AQP4) blockade can be caused by various factors, including genetic mutations, autoimmune responses, and cellular signaling pathways. Blockade can also be induced by certain drugs and cellular stress.
Here's a more detailed breakdown:
Mutations in the AQP4 gene can impair its water permeability, potentially leading to a functional block. [6]
Autoimmune Responses (Rare):
In Neuromyelitis Optica Spectrum Disorder (NMOSD), anti-AQP4 antibodies attack and damage the central nervous system, leading to inflammation and AQP4 dysfunction. [7,8]
Cellular Signaling:
Phosphorylation of AQP4 at specific sites, like Ser180, can lead to its inhibition, while phosphorylation at other sites, like Ser111, can activate it. [9]
Calmodulin Interaction:
Calmodulin directly binds to the carboxyl terminus of AQP4, influencing its localization and potentially causing a conformational change that affects water transport. Calmodulin directly binds the AQP4 carboxyl terminus, causing a specific conformational change and driving AQP4 cell-surface localization. Inhibition of calmodulin in a rat spinal cord injury model with the licensed drug trifluoperazine inhibited AQP4 localization to the blood-spinal cord barrier, ablated CNS edema, and led to accelerated functional recovery compared with untreated animals. We propose that targeting the mechanism of calmodulin-mediated cell-surface localization of AQP4 is a viable strategy for development of CNS edema therapies. [10]
Inhibition of AQP4 can alter the osmotic stress in the extracellular space surrounding microglia, potentially leading to their activation and inflammation. However, the mechanism behind the decrease of the AQP4 and activation of microglia is less obvious and still unknown. One possible mechanism behind the changes observed in post-traumatic or ischemic microglia activation and cytokine release in response to AQP4 downregulation or inhibition may be partly due to the presence of stretch-activated Cl- channels expressed in microglia. Stretch-activated/swelling-activated Cl- channels are activated by osmotic stress. It has been observed that the activation of these channels contributes the maintenance of the non-activated (ramified) phenotype of microglia . Because AQP4 is responsible for water transport, inhibition of AQP4 either through genetic deletion or siRNA will alter the osmotic stress within the extracellular space surrounding the microglia, changing the activation status of the swelling activated chloride channels, resulting in microglial activation. Another possibility lies in the cross-talk that occurs between astrogliosis and microglial activation. It is possible that the decreased extent of injury-induced reactive astrogliosis as a result of knocking down AQP4 caused increased microglial activity. [11]
IL-1β Stimulation:
IL-1β, a pro-inflammatory cytokine, can induce AQP4 expression in astrocytes, but blocking IL-1β can decrease AQP4-related edema. Elevated levels of IL-10, TNF-α, IL-1β, and IL-2 are found after middle cerebral artery occlusion in the rat brain. An increase in TNF-α, IL-6, and IL-1β is found after transient cerebral ischemia. The surge of inflammatory cytokines in the brain can be detected within an hour after injury. In astrocytes, IL-1β is a potent activator of NFκB, which leads to increased AQP4 transcription. Ito et al. confirmed that IL-1β was a potent inducer of AQP4 expression in astrocytes and that this induction was mediated by NF-κB activation. Another cytokine, TNF-α, is also a potent activator of NFκB . Interestingly, TNF-α seems to interact with IL-1 in a positive-feedback system to induce the spread of inflammation. This positive feedback loop can cause a sustained elevation of cytokines. The up-regulation of AQP4 by TNF-α has been confirmed in an epithelial cell line . In addition, VEGF has been found to induce up-regulation of Aqp4 mRNA in vivo. VEGF promotes angiogenesis and increases vascular permeability in the brain, and its transcript starts to increase as early as 2 hours after ischemic injury. Like the opposing effects of AQP4 in different edematous phases post-injury, VEGF injection has a detrimental role if injected 1 hour after injury, but promotes recovery when injected 48 hours after injury. We conjecture that the sustained rise of AQP4 levels observed in brain pathologies is mainly caused by the elevation of cytokines during neuroinflammation. [12]
Certain anti-epileptic drugs, like topiramate, have been reported to block AQP4 function.
Conditions like traumatic brain injury, stroke, and ischemia can disrupt AQP4 function and localization.
Sleep disruption can affect the glymphatic system, a pathway involving AQP4 in brain waste clearance, and impairing this function. Recently, we have demonstrated that AQP4 localization is also dynamically regulated at the subcellular level, affecting membrane water permeability. Ageing, cerebrovascular disease, traumatic CNS injury, and sleep disruption are established and emerging risk factors in developing neurodegeneration, and in animal models of each, impairment of glymphatic function is associated with changes in perivascular AQP4 localization. CNS oedema is caused by passive water influx through AQP4 in response to osmotic imbalances. We have demonstrated that reducing dynamic relocalization of AQP4 to the BSCB/BBB reduces CNS oedema and accelerates functional recovery in rodent models. Given the difficulties in developing pore-blocking AQP4 inhibitors, targeting AQP4 subcellular localization opens up new treatment avenues for CNS oedema, neurovascular and neurodegenerative diseases, and provides a framework to address fundamental questions about water homeostasis in health and disease. [14]
Changes in mitochondrial function at astrocyte end-feet can affect AQP4 expression and water transport. The increase in pathological mitochondria at the astrocyte end-feet and the decrease in normal mitochondria will inevitably lead to the dysfunction of water and substance exchange, which may also be one of the mechanisms for the decreased expression of perivascular AQP4. [15]
Circulating IgG1 antibodies against AQP4 are a hallmark of Neuromyelitis Optica (NMO).
Aquaporin-4 and Brain Edema / Stroke: Methylene Blue Inhibits AQP-4
“Methylene blue (MB) was found to exert neuroprotective effect on different brain diseases, such as ischemic stroke. This study assessed the MB effects on ischemia induced brain edema and its role in the inhibition of aquaporin 4 (AQP4) and metabotropic glutamate receptor 5 (mGluR5) expression…. MB remarkably decreased the volumes of T2WI and ADC lesions, as well as the cerebral swelling. Consistently, MB treatment significantly decreased GFAP, mGluR5 and AQP4 expression at 48 h after stroke. In the cultivated primary ASTs, OGD/R and DHPG significantly increased ASTs volume as well as AQP4 expression, which was reversed by MB and fenobam treatment. The obtained results highlight that MB decreases the post-ischemic brain swelling by regulating the activation of AQP4 and mGluR5, suggesting potential applications of MB on clinical ischemic stroke treatment.” [16]
“Brain edema is a common and serious complication of ischemic stroke with limited effective treatment. We previously reported that methylene blue (MB) attenuated ischemic brain edema in rats, but the underlying mechanisms remained unknown. Aquaporin 4 (AQP4) in astrocytes plays a key role in brain edema. We also found that extracellular signal-regulated kinase 1/2 (ERK1/2) activation was involved in the regulation of AQP4 expression in astrocytes. In the present study, we investigated whether AQP4 and ERK1/2 were involved in the protective effect of MB against cerebral edema…We found that MB infusion significantly ameliorated cytotoxic brain edema at 2.5 and 48 h after tMCAO and decreased vasogenic brain edema at 48 h after tMCAO. In addition, MB infusion blocked the AQP4 increases and ERK1/2 activation in the cerebral cortex in ischemic penumbra at 48 h after tMCAO. In a cell swelling model established in cultured rat astrocyte exposed to glutamate (1 mM), we consistently found that MB (10 μM) attenuated cell swelling, AQP4 increases and ERK1/2 activation. Moreover, the ERK1/2 inhibitor U0126 (10 μM) had the similar effects as MB. These results demonstrate that MB improves brain edema and astrocyte swelling, which may be mediated by the inhibition of AQP4 expression via ERK1/2 pathway, suggesting that MB may be a potential choice for the treatment of brain edema.” [17]
Aquaporin-4 and Brain Edema / Stroke: Methylene Blue Inhibits AQP-4 (rs397507547)
Aquaporins (AQPs) play a physiological role in several organs and tissues, and their alteration is associated with disorders of water regulation. The identification of molecular interactions, which are crucial in determining the rate of water flux through the channel, is of pivotal role for the discovery of molecules able to target those interactions and therefore to be used for pathologies ascribable to an altered AQP-dependent water balance. In the present study, a mutational screening of human aquaporin-4 (AQP4) gene was performed on subjects with variable degrees of hearing loss. One heterozygous missense mutation was identified in a Spanish sporadic case, leading to an Asp/Glu amino acid substitution at position 184 (D184E). A BLAST analysis revealed that the amino acid D184 is conserved across species, consistently with a crucial role in the structure/function of AQP4 water channels. The mutation induces a significant reduction in water permeability as measured by the Xenopus laevis oocytes swelling assay and by the use of mammalian cells by total internal reflection microscopy. By Western blot, immunofluorescence and 2D Blue Native/SDS-PAGE we show that the reduction in water permeability is not ascribable to a reduced expression of AQP4 mutant protein or to its incorrect plasma membrane targeting and aggregation into orthogonal arrays of particles. Molecular dynamics simulation provided a molecular explanation of the mechanism whereby the mutation induces a loss of function of the channel. Substituting glutamate for aspartate affects the mobility of the D loop, which acquires a higher propensity to equilibrate in a "closed conformation", thus affecting the rate of water flux. We speculate that this mutation, combined with other genetic defects or concurrently with certain environmental stimuli, could confer a higher susceptibility to deafness.” [6]
Aquaporin’s and Alzheimer’s
“The central nervous system is highly dependent on water, and disturbances in water homeostasis can have a significant impact on its normal functions. The regulation of water balance is, at least in part, carried out via specialized water channels called aquaporins. In the central nervous system, two major aquaporins (AQPs), AQP1 and AQP4, and their potential involvements have been long implicated in the pathophysiology of many brain disorders such as brain edema and Neuromyelitis optica. In addition to these diseases, there is growing attention to the involvement of AQPs in the removal of waste products in Alzheimer’s disease (AD). This indicates that targeting fluid homeostasis is a novel and attractive approach for AD.
AQP1 is the second most abundant water channel in the brain and is mainly found on the apical surface of the choroid plexus. AQP1 in the choroid plexus is involved in CSF secretion, which is important for maintaining proper volume and pressure of the CSF. Although AQP1 has not been extensively studied in the context of AD, evidence suggests that it may play a role in the pathogenesis of the disease. There are studies showing that AQP1 expression is upregulated in reactive astrocytes surrounding Aβ plaques of AD patients.
Studies have suggested that AQP4 plays a significant role in the pathogenesis of AD. In particular, its involvement in the glymphatic system is currently a very active and popular area of research in the field of neuroscience.
The crucial roles of AQP4 on AD pathogenesis are supported by the observation that a lack of AQP4 exacerbates AD pathology in animal models. However, as reviewed in this article, the roles of AQPs in the CNS are complex and multifaceted, and the exact mechanisms, as well as whether they influence AD pathogenesis, depend on the glymphatic system, which needs to be further explored.
Although arterial pulsation and AQP4 are important factors in the regulation of glymphatic flow, many other factors can also influence this process as well.
Another critical question from a therapeutic standpoint is whether the glymphatic system can be therapeutically targeted to slow or prevent the progression of AD. Although AQPs, especially AQP4 have emerged as a promising therapeutic target in AD, further research is required to determine the feasibility and effectiveness of this approach. In addition to directly facilitating its channel function, regulating the trafficking of AQP4 to plasma membrane levels is another strategy. In fact, a recent study using high-throughput screening and counter-screening demonstrated that small molecule compounds that facilitate a translational readthrough of AQP4 can enhance the clearance of Aβ in vivo. The development of suitable in vitro models to screen and validate the pharmacological regulation of AQP4 function will significantly facilitate translational research in this field. [19]
Aquaporin-4 Genetic Mutations and Parkinson’s (rs 7240333)
“Growing evidence suggests that the glymphatic system, driven by aquaporin-4 (AQP4) water channels, plays a key role in Parkinson’s disease (PD). We examined the impact of specific AQP4 variants on glymphatic function using diffusion tensor imaging along the perivascular space (DTI-ALPS), and explored potential mechanisms underlying motor symptom severity and progression in PD. PD participants exhibited lower DTI-ALPS indices compared to controls. Reduced DTI-ALPS at baseline was linked to more severe motor symptoms and faster longitudinal motor decline, as assessed by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale, Part III (MDS-UPDRS III). One specific AQP4 variant was associated with decreased DTI-ALPS and increased MDS-UPDRS III scores, with DTI-ALPS mediating this relationship at baseline and follow-up. Some variants exhibited indirect protective effects on motor symptoms via enhanced glymphatic function. These findings indicate that AQP4 polymorphisms contribute to glymphatic dysfunction and motor progression in PD, supporting strategies for disease modification.”[20]
Summary
Blue Light Therapy may be something to consider in cases where glymphatic drainage issues are suspected or confirmed through testing. Testing for anti bodies related to Aquaporin-4 can be informative, as can genetic testing for specific variants / mutations on AQP-4. Although the Alzheimer’s and Parkinson’s testing to date is on mice, the results certainly look interesting. Blue light devices are readily available and inexpensive.
References:
[1] “Blue-Light Therapy following Mild Traumatic Brain Injury: Effects on White Matter Water Diffusion in the Brain”, By Baja, et. al., Frontiers In Neurology, 21 November 2017. Section Neurotrauma. Volume 8 - 2017 | https://doi.org/10.3389/fneur.2017.00616[2] “Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer’s disease”, By Wu, et. al. Nature Communications, . 2025 Jan 2;16:63. doi:10.1038/s41467-024-55678-w[3] “Aquaporin-4 in glymphatic system, and its implication for central nervous system disorders”, By Peng, et. al. Neurobiol Dis. 2023 Apr:179:106035. doi: 10.1016/j.nbd.2023.106035.Epub 2023 Feb 15.[4] “Loss of aquaporin-4 results in glymphatic system dysfunction via brain-wide interstitial fluid stagnation”, By Gomolka, et. al. eLife . 2023 Feb 9;12:e82232. doi:10.7554/eLife.82232. PMCID: PMC9995113 PMID: 36757363[5] Mechanisms Underlying Aquaporin-4 Subcellular Mislocalization in Epilepsy, By Szu, et. al. Front Cell Neurosci . 2022 Jun 6;16:900588. doi: 10.3389/fncel.2022.900588[6] D184E mutation in aquaporin-4 gene impairs water permeability and links to deafness, by Nichia, et. al. Neuroscience . 2011 Dec 1:197:80-8. doi: 10.1016/j.neuroscience.2011.09.023. Epub 2011 Sep 16. PMID: 21952128. DOI: 10.1016/j.neuroscience.2011.09.023[7] Signs, symptoms, and damage of NMOSD | Navigating NMOSD[8] Eculizumab in Aquaporin-4–Positive Neuromyelitis Optica Spectrum Disorder, By Pitock, et. al. The New England Journal of Medicine. Published May 2, 2019N Engl J Med 2019;381:614-625. DOI: 10.1056/NEJMoa1900866. VOL. 381 NO. 7[9] Physiological Roles of Aquaporin-4 in Brain, By Erlend A. Nagelhus and Ole P. Ottersen. Physiological Reviews. 01 Oct 2013https://doi.org/10.1152/physrev.00011.2013[10] Targeting Aquaporin-4 Subcellular Localization to Treat Central Nervous System Edema, By Kitchen, et. al. Cell, Volume 181, Issue 4p784-799.e19May 14, 2020 . [11] Aquaporin 4: a player in cerebral edema and neuroinflammation, By Andrew M Fukuda J Neuroinflammation . 2012 Dec 27;9:279. doi: 10.1186/1742-2094-9-279. PMCID: PMC3552817 PMID: 23270503[12] Dynamic regulation of aquaporin-4 water channels in neurological disorders, By Hsu, et. al. Croat Med J . 2015 Oct;56(5):401–421. doi: 10.3325/cmj.2015.56.401. PMCID: PMC4655926 PMID: 26526878[13] Aquaporin-4 Water Channel in the Brain and Its Implication for Health and Disease, By Mader, et. al. Cells . 2019 Jan 27;8(2):90. doi: 10.3390/cells8020090. PMCID: PMC6406241 PMID: 30691235[14] Emerging roles for dynamic aquaporin-4 subcellular relocalization in CNS water homeostasis , By Mootaz M Salman , et. al. Brain, Volume 145, Issue 1, January 2022, Pages 64–75, https://doi.org/10.1093/brain/awab311[15] Aquaporin-4 and Cognitive Disorders, By Wang, et. al. Aging Dis . 2022 Feb 1;13(1):61–72. doi: 10.14336/AD.2021.0731. PMCID: PMC8782559 PMID: 35111362[16] The protective effects of methylene blue on astrocytic swelling after cerebral ischemia-reperfusion injuries are mediated by Aquaporin-4 and metabotropic glutamate receptor 5 activation. By Yu Lai, et. al. Heliyon. . 2024 Apr 12;10(8):e29483. doi: 10.1016/j.heliyon.2024.e29483. PMCID: PMC11031768 PMID: 38644842[17] Methylene blue ameliorates brain edema in rats with experimental ischemic stroke via inhibiting aquaporin 4 expression. By Zhong-fang Shi, et. al. nature. acta pharmacologica sinica. Published: 14 July 2020. Acta Pharmacologica Sinica volume 42, pages382–392 (2021)[19] Multifaceted Roles of Aquaporins in the Pathogenesis of Alzheimer’s Disease. by Kaoru Yamada. Department of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. Int. J. Mol. Sci. 2023, 24(7), 6528; https://doi.org/10.3390/ijms24076528[20] The effects of aquaporin-4 polymorphisms on glymphatic function and motor symptoms in Parkinson’s disease. By Jianmei Qin, nature. npj parkinson's disease. Published: 08 October 2025. npj Parkinson's Disease volume 11, Article number: 288 (2025).