Cerebrospinal Fluid Level of Aquaporin4: A New Window on Glymphatic System Involvement in Neurodegenerative Disease?

Arighi, Andrea; Cristofori, Andrea Di; Fenoglio, Chiara; Borsa, Stefano; D’Anca, Marianna; Fumagalli, Giorgio; Locatelli, Marco; Carrabba, Giorgio; Pietroboni, Anna M.; Ghezzi, Laura; Carandini, Tiziana; Colombi, A; Scarioni, Marta; Riz, Milena A. De; Serpente, María; Rampini, Paolo; Scarpini, Elio; Galimberti, Daniela

doi:10.3233/jad-190119

Cited by 22 publications

(21 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…41 We have herein identified increased levels of AQP4 in CSF from AD patients compared with controls in four independent cohorts. In contrast, Arighi et al 42 found lower levels of AQP4 in CSF in AD patients compared with controls, although in a small sample set (AD n = 11, controls n = 9). Further studies are needed to explain the potential role of CSF AQP4 in AD and the discordant results in our study compared with others.…”

Section: Discussionmentioning

confidence: 74%

Multi‐cohort profiling reveals elevated CSF levels of brain‐enriched proteins in Alzheimer’s disease

Bergström

Remnestål

Yousef

et al. 2021

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Objective: Decreased amyloid beta (Ab) 42 together with increased tau and phospho-tau in cerebrospinal fluid (CSF) is indicative of Alzheimer's disease (AD). However, the molecular pathophysiology underlying the slowly progressive cognitive decline observed in AD is not fully understood and it is not known what other CSF biomarkers may be altered in early disease stages. Methods: We utilized an antibody-based suspension bead array to analyze levels of 216 proteins in CSF from AD patients, patients with mild cognitive impairment (MCI), and controls from two independent cohorts collected within the AETI-ONOMY consortium. Two additional cohorts from Sweden were used for biological verification. Results: Six proteins, amphiphysin (AMPH), aquaporin 4 (AQP4), cAMP-regulated phosphoprotein 21 (ARPP21), growth-associated protein 43 (GAP43), neurofilament medium polypeptide (NEFM), and synuclein beta (SNCB) were found at increased levels in CSF from AD patients compared with controls. Next, we used CSF levels of Ab42 and tau for the stratification of the MCI patients and observed increased levels of AMPH, AQP4, ARPP21, GAP43, and SNCB in the MCI subgroups with abnormal tau levels compared with controls. Further characterization revealed strong to moderate correlations between these five proteins and tau concentrations. Interpretation: In conclusion, we report six extensively replicated candidate biomarkers with the potential to reflect disease development. Continued evaluation of these proteins will determine to what extent they can aid in the discrimination of MCI patients with and without an underlying AD etiology, and if they have the potential to contribute to a better understanding of the AD continuum.

show abstract

Section: Discussionmentioning

confidence: 74%

Multi‐cohort profiling reveals elevated CSF levels of brain‐enriched proteins in Alzheimer’s disease

Bergström

Remnestål

Yousef

et al. 2021

Ann Clin Transl Neurol

View full text Add to dashboard Cite

show abstract

“…A specific biomarker for iNPH is therefore required to improve diagnostic accuracy. AQP proteins in human CSF have been previously analyzed to find biomarkers for certain neurological diseases [28][29][30][31]. Given that recent findings have revealed AQP1 and AQP4 as key players in CSF homeostasis and that disturbance of their expression in the brain is an indication of the onset of iNPH [9,13], in the present study we evaluated the presence of these proteins in the CSF of patients with this disease (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…We used two specific ELISA kits to determine the presence of AQP1 and AQP4 in CSF [28][29][30][31][32]. The results demonstrated that neither of these two proteins were detectable at significant levels in most of the analyzed CSF samples (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Evaluation of aquaporins in the cerebrospinal fluid in patients with idiopathic normal pressure hydrocephalus

et al. 2021

View full text Add to dashboard Cite

Brain aquaporin 1 (AQP1) and AQP4 are involved in cerebrospinal fluid (CSF) homeostasis and might participate in the origin of hydrocephalus. Studies have shown alterations of perivascular AQP4 expression in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer’s disease (AD). Due to the overlapping of clinical signs between iNPH and certain neurological conditions, mainly AD, specific biomarkers might improve the diagnostic accuracy for iNPH. The goal of the present study was to analyze and quantify the presence of AQP1 and AQP4 in the CSF of patients with iNPH and AD to determine whether these proteins can be used as biomarkers of iNPH. We examined AQP1 and AQP4 protein levels in the CSF of 179 participants (88 women) classified into 5 groups: possible iNPH (81 participants), hydrocephalus associated with other neurological disorders (13 participants), AD (41 participants), non-AD dementia (32 participants) and healthy controls (12 participants). We recorded each participant’s demographic and clinical variables and indicated, when available in the clinical history, the record of cardiovascular and respiratory complications. An ELISA showed virtually no AQP content in the CSF. Information on the vascular risk factors (available for 61 patients) confirmed some type of vascular risk factor in 86% of the patients with possible iNPH and 58% of the patients with AD. In conclusion, the ELISA analysis showed insufficient sensitivity to detect the presence of AQP1 and AQP4 in CSF, ruling out the possible use of these proteins as biomarkers for diagnosing iNPH.

show abstract

“…Such pathway is also referred as "glymphatic system" since the draining space resembles the peripheral lymphatic system. The glymphatic system enables cerebrospinal fluid (CSF) to enter the brain via periarterial spaces and move into the interstitium via aquaporin-4 (AQP4) located in the endfeet of perivascular astrocytes; it also drives the perivenous drainage of interstitial fluid (ISF) and its solutes, thereby clearing the brain of metabolic waste [8][9][10][11][12]. AQP4 is an important factor affecting the glymphatic system's functionality [6].…”

Section: Introductionmentioning

confidence: 99%

Electroacupuncture Improves Clearance of Amyloid-β through the Glymphatic System in the SAMP8 Mouse Model of Alzheimer’s Disease

Liang

Zhang

et al. 2021

Neural Plasticity

View full text Add to dashboard Cite

Background. Memory loss and cognitive impairment characterize the neurodegenerative disorder, Alzheimer’s disease (AD). Amyloid-β (Aβ) is the key factor that triggers the course of AD, and reducing the deposition of Aβ in the brain has been considered as a potential target for the treatment of AD. In clinical and animal studies, electroacupuncture (EA) has been shown to be an effective treatment for AD. In recent years, substantial evidence has accumulated suggesting the important role of the glymphatic system in Aβ clearance. Objective. The purpose of this study was to explore whether EA modifies the accumulation of Aβ through the glymphatic system and may thus be applied to alleviate cognitive impairments. Methods. Seven-month-old SAMP8 mice were randomized into a control group (Pc) and an electroacupuncture group (Pe). Age-matched SAMR1 mice were used as normal controls (Rc). Mice in the Pe group were stimulated on Baihui (GV20) and Yintang (GV29) for 10 min and then pricked at Shuigou (GV26) for ten times. EA treatment lasted for 8 weeks. In each week, EA would be applied once a day for the first five consecutive days and ceased at the remaining two days. After EA treatment, Morris water maze (MWM) test was used to evaluate the cognitive function; HE and Nissl staining was performed to observe the brain histomorphology; ELISA, contrast-enhanced MRI, and immunofluorescence were applied to explore the mechanisms underlying EA effects from Aβ accumulation, glymphatic system function, reactivity of astrocytes, and AQP4 polarization, respectively. Results. This EA regime could improve cognition and alleviate neuropathological damage to brain tissue. And EA treatment might reduce Aβ accumulation, enhance paravascular influx in the glymphatic system, inhibit the reactivity of astrocytes, and improve AQP4 polarity. Conclusion. EA treatment might reduce Aβ accumulation from the brain via improving clearance performance of the glymphatic system and thereby alleviating cognitive impairment.

show abstract

Cerebrospinal Fluid Level of Aquaporin4: A New Window on Glymphatic System Involvement in Neurodegenerative Disease?

Cited by 22 publications

References 33 publications

Multi‐cohort profiling reveals elevated CSF levels of brain‐enriched proteins in Alzheimer’s disease

Multi‐cohort profiling reveals elevated CSF levels of brain‐enriched proteins in Alzheimer’s disease

Evaluation of aquaporins in the cerebrospinal fluid in patients with idiopathic normal pressure hydrocephalus

Electroacupuncture Improves Clearance of Amyloid-β through the Glymphatic System in the SAMP8 Mouse Model of Alzheimer’s Disease

Contact Info

Product

Resources

About