title: Reduced CSF Water Influx in Alzheimer's Disease Supporting the β-Amyloid Clearance Hypothesis.
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 [15O]H2O 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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  UMIN Clinical Trials Registry UMIN000011939.
authors.affiliation: Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Hironaka
authors.initials: H
authors.lastname: Igarashi
authors.affiliation: Department of Molecular Genetics, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Kensaku
authors.initials: K
authors.lastname: Kasuga
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Niigata, Niigata, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yokoyama
authors.affiliation: Department of Molecular Genetics, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ikeuchi
authors.affiliation: Department of Neurology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Masatoyo
authors.initials: M
authors.lastname: Nishizawa
authors.affiliation: Department of Neurology, University of California Davis, Davis, California, United States of America.
authors.forename: Ingrid L
authors.initials: IL
authors.lastname: Kwee
authors.affiliation: Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, Niigata, Japan; Department of Neurology, University of California Davis, Davis, California, United States of America.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakada
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001834:Body Water / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014882:Water-Electrolyte Balance
chemical_list: D016229:Amyloid beta-Peptides