Water influx into cerebrospinal fluid is significantly reduced in senile plaque bearing transgenic mice, supporting beta-amyloid clearance hypothesis of Alzheimer’s disease

Abstract

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.

Keywords:

• MRI
• JJVCPE
• Aquaporin
• Virchow–Robin space
• Interstitial flow

Acknowledgements

The work was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology (Japan) and University of Niigata.