Water influx into cerebrospinal fluid is significantly reduced in senile plaque bearing transgenic mice, supporting beta-amyloid clearance hypothesis of Alzheimer’s disease
Open accessAbstract
Recent studies on cerebrospinal fluid (CSF) homeostasis emphasize the importance of water influx into the peri-capillary (Virchow-Robin) space through aquaporin 4 (AQP-4). This water flow is believed to have the functionality equivalent to the systemic lymphatic system and plays a critical role in beta-amyloid clearance. Using a newly developed molecular imaging technique capable of tracing water molecules, in vivo, water influx into the CSF was quantitatively analyzed in senile plaque (SP) bearing transgenic Alzheimer's disease (AD) model mice. The results unequivocally demonstrated that water influx into CSF is significantly impaired in SP-bearing transgenic mice, the degree of which being virtually identical to that previously observed in AQP-4 knockout mice. The study strongly indicates that disturbance in AQP-4-based water flow and, hence, impairment in beta-amyloid clearance play a significant role in SP formation.
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Astrocytes are involved in the clearance of Aβ through the BBB via the AQP4 channels expressed in their end feet and are also able to phagocytose amyloid.
“astrocytes are involved in the clearance of Aβ through the BBB via the AQP4 channels expressed in their end feet and are also able to phagocytose amyloid [6, 34, 35].”
From Pharmacological ablation of astrocytes reduces Aβ degradation and synaptic connectivity in an ex vivo model of Alzheimer’s disease (2021) · cites this paper as [35]
The Introduction identifies AQP-4 on astrocyte end feet and links AQP-4-regulated CSF flow to beta-amyloid clearance. The Discussion describes drainage toward the CSF through perivascular spaces, not Aβ clearance through the BBB. Neither section says astrocytes phagocytose amyloid. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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Lymphatic drainage of the brain and the pathophysiology of neurological disease
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Mechanisms of Aβ Clearance and Degradation by Glial Cells
Ries, M., & Sastre, M. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00160 · Cited by 527 · see citing works
“High expression of the channel aquaporin 4 (AQP-4) at the astrocyte end feet is thought to help solute clearance due to its role in water transport (Igarashi et al., 2014).”
BackgroundWięckowska-Gacek, A., Mietelska-Porowska, A., Wydrych, M., & Wojda, U. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101397 · Cited by 343 · see citing works
Davis, N., Mota, B. C., Stead, L., Palmer, E. O. C., Lombardero, L., Rodríguez-Puertas, R., de Paola, V., Barnes, S. J., & Sastre, M. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02117-y · Cited by 65 · see citing works
- Authors
- Igarashi, H., Suzuki, Y., Kwee, I. L., & Nakada, T.
- Affiliations
- Niigata University (JP)
- University of California, Davis (US)
- Brain Research Institute, Niigata University (JP)
- Corresponding author
- Nakada, Tsutomu
- Venue
- Neurological Research
- Publisher
- Informa UK Limited
- Published
- 2014-08
- Volume
- 36
- Issue
- 12
- Pages
- 1094-1098
- ISSN
- 0161-6412 (ISSN-L)
- 1743-1328
- PMC
- PMC4188033
- OpenAlex
- W2089424953
- Cited by
- 43
- References
- 2
- Citations by year
- 2026: 4 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 3 · 2014: 1
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Neurological Research (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (25461310)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- cerebrospinal fluid, water inflow, aquaporin-4, amyloid plaques, amyloid-beta clearance, Alzheimer's disease, perivascular spaces, transgenic mice
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Humans, Male, Mice, Transgenic, Magnetic Resonance Spectroscopy, Oxygen Isotopes, Water, Amyloid beta-Protein Precursor, Mice, Presenilin-1, Plaque, Amyloid
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