Reduced CSF water influx in Alzheimer's disease supporting the β-amyloid clearance hypothesis

Yuji Suzuki, Yukihiro Nakamura, Kenichi Yamada, Hironaka Igarashi, Kensaku Kasuga, Yuichi Yokoyama, Takeshi Ikeuchi, Masatoyo Nishizawa, Ingrid Kwee, Tsutomu Nakada

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13 Scopus citations

Abstract

Objective: To investigate whether water influx into cerebrospinal fluid (CSF) space is reduced in Alzheimer's patients as previously shown in the transgenic mouse model for Alzheimer's disease. Methods: Ten normal young volunteers (young control, 21-30 years old), ten normal senior volunteers (senior control, 60-78 years old, MMSE ≥ 29), and ten Alzheimer's disease (AD) patients (study group, 59-84 years old, MMSE: 13-19) participated in this study. All AD patients were diagnosed by neurologists specializing in dementia based on DSM-IV criteria. CSF dynamics were analyzed using positron emission tomography (PET) following an intravenous injection of 1,000 MBq [<sup>15</sup>O]H<sup>2</sup>O synthesized on-line. Results: Water influx into CSF space in AD patients, expressed as influx ratio, (0.755 ± 0.089) was significantly reduced compared to young controls (1.357 ± 0.185; p < 0.001) and also compared to normal senior controls (0.981 ± 0.253, p < 0.05). Influx ratio in normal senior controls was significantly reduced compared to young controls (p < 0.01). Conclusion: Water influx into the CSF is significantly reduced in AD patients. β-amyloid clearance has been shown to be dependent on interstitial flow and CSF production. The current study indicates that reduction in water influx into the CSF may disturb the clearance rate of β-amyloid, and therefore be linked to the pathogenesis of AD.

Original languageEnglish (US)
Article numbere0123708
JournalPLoS One
Volume10
Issue number5
DOIs
StatePublished - May 6 2015

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Suzuki, Y., Nakamura, Y., Yamada, K., Igarashi, H., Kasuga, K., Yokoyama, Y., Ikeuchi, T., Nishizawa, M., Kwee, I., & Nakada, T. (2015). Reduced CSF water influx in Alzheimer's disease supporting the β-amyloid clearance hypothesis. PLoS One, 10(5), [e0123708]. https://doi.org/10.1371/journal.pone.0123708