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. 2022 Sep 17;14(1):135.
doi: 10.1186/s13195-022-01077-6.

Aquaporin-4 cerebrospinal fluid levels are higher in neurodegenerative dementia: looking at glymphatic system dysregulation

Andrea Arighi  1 , Marina Arcaro  2 , Giorgio Giulio Fumagalli  2 , Tiziana Carandini  2 , Anna Margherita Pietroboni  2 , Luca Sacchi  2   3 , Chiara Fenoglio  3 , Maria Serpente  2 , Federica Sorrentino  3 , Giovanni Isgrò  2 , Federico Turkheimer  4 , Elio Scarpini  2   3 , Daniela Galimberti  2   3
Affiliations

Aquaporin-4 cerebrospinal fluid levels are higher in neurodegenerative dementia: looking at glymphatic system dysregulation

Andrea Arighi et al. Alzheimers Res Ther. .

Abstract

Aquaporin-4 (AQP4) is a channel protein that plays a fundamental role in glymphatic system, a newly described pathway for fluid exchange in the central nervous system, as well as a central figure in a fascinating new theory for the pathophysiology of neurodegenerative diseases such as Alzheimer's disease (AD) and frontotemporal dementia (FTD). In this study, cerebrospinal fluid (CSF) concentration of AQP4, amyloid-β, total tau and P-tau were determined in 103 CSF samples from patients affected by neurodegenerative dementias (AD and FTD) or psychiatric diseases and 21 controls. Significantly higher levels of AQP4 were found in AD and FTD patients compared to subjects not affected by neurodegenerative diseases, and a significant, positive correlation between AQP4 and total tau levels was found. This evidence may pave the way for future studies focused on the role of this channel protein in the clinical assessment of the glymphatic function and degree of neurodegeneration.

Keywords: Alzheimer’s disease; Amyloid-β; Aquaporin 4; Cerebrospinal fluid; Frontotemporal dementia; Glymphatic system.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
On the left, box plot representing cerebrospinal fluid (CSF) aquaporin 4 (AQP4) levels in the diagnostic groups: Alzheimer’s disease (AD), frontotemporal dementia (FTD), mild cognitive impairment (MCI), psychiatric disorder (Psy), and control group (Con). On the right, box plot with three-group classification: patients affected by neurodegenerative disease (Deg), patients with neurological or psychiatric not degenerative disease (Non-Deg), and controls (Con)
Fig. 2
Fig. 2
Box plot representing cerebrospinal fluid (CSF) aquaporin 4 (AQP4) levels (on the left) and frequency analysis (on the right) in the two main groups: patients affected by neurodegenerative diseases (Deg), and patients not affected by degenerative diseases (Non-Deg + Con groups). The bar plot shows the number of patients with high and low AQP4 levels distributed in the two main groups (light for Deg and dark for Non-Deg + Con)
Fig. 3
Fig. 3
Box plots representing cerebrospinal fluid (CSF) aquaporin 4 (AQP4) levels in the three parameters of ATN classification: A + / − (according to β amyloid CSF levels) on the left, T + / − (according to P-Tau CSF levels) in the middle, and N + / − (according to total Tau levels) on the right. The only significant difference is in the levels of AQP4 in N+ compared to N−
Fig. 4
Fig. 4
Multiparametric linear regression comparing Log10 cerebrospinal fluid (CSF) aquaporin 4 (AQP4) levels (y-axis) with β-amyloid 1–42 (first line, left), β-amyloid 1–40 (first line, right), total tau (second line, left), and phosphorylated tau (second line, right)
See this image and copyright information in PMC

References

    1. Wang Z, Ying Z, Bosy-Westphal A, Zhang J, Heller M, Later W, Heymsfield SB, Müller MJ. Evaluation of specific metabolic rates of major organs and tissues: comparison between men and women. Am J Hum Biol. 2011;23(3):333–8. doi: 10.1002/ajhb.21137. - DOI - PMC - PubMed
    1. Thibaudeau TA, Anderson RT, Smith DM. A common mechanism of proteasome impairment by neurodegenerative disease-associated oligomers. Nat Commun. 2018;9(1):1097. doi: 10.1038/s41467-018-03509-0.PMID:29545515;PMCID:PMC5854577. - DOI - PMC - PubMed
    1. Tarasoff-Conway JM, Carare RO, Osorio RS, Glodzik L, Butler T, Fieremans E, Axel L, Rusinek H, Nicholson C, Zlokovic BV, Frangione B, Blennow K, Ménard J, Zetterberg H, Wisniewski T, de Leon MJ. Clearance systems in the brain-implications for Alzheimer disease. Nat Rev Neurol. 2015;11(8):457–70. doi: 10.1038/nrneurol.2015.119. - DOI - PMC - PubMed
    1. Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med. 2012;4(147):147ra111. doi: 10.1126/scitranslmed.3003748. - DOI - PMC - PubMed
    1. Mestre H, Hablitz LM, Xavier AL, Feng W, Zou W, Pu T, Monai H, Murlidharan G, Castellanos Rivera RM, Simon MJ, Pike MM, Plá V, Du T, Kress BT, Wang X, Plog BA, Thrane AS, Lundgaard I, Abe Y, Yasui M, Thomas JH, Xiao M, Hirase H, Asokan A, Iliff JJ, Nedergaard M. Aquaporin-4-dependent glymphatic solute transport in the rodent brain. Elife. 2018;18(7):e40070. doi: 10.7554/eLife.40070. - DOI - PMC - PubMed

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