Blood Cerebrospinal Fluid Barrier Function Disturbance Can Be Followed by Amyloid-β Accumulation

Abstract

Background: Elucidation of the mechanism of amyloid-β accumulation plays an important role in therapeutic strategies for Alzheimer’s disease (AD). The aim of this study is to elucidate the relationship between the function of the blood–cerebrospinal fluid barrier (BCSFB) and the clearance of amyloid-β (Aβ). Methods: Twenty-five normal older adult volunteers (60–81 years old) participated in this PET study for clarifying the relationship between interstitial water flow and Aβ accumulation. Water dynamics were analyzed using two indices in [15O]H2O PET, the influx ratio (IR) and drain rate (DR), and Aβ accumulation was assessed qualitatively by [18F]flutemetamol PET. Results: [15O]H2O PET examinations conducted initially and after 2 years showed no significant changes in both indices over the 2-year period (IR: 1.03 ± 0.21 and 1.02 ± 0.20, DR: 1.74 ± 0.43 and 1.67 ± 0.47, respectively). In [18F]flutemetamol PET, on the other hand, one of the 25 participants showed positive results and two showed positive changes after 2 years. In these three participants, the two indices of water dynamics showed low values at both periods (IR: 0.60 ± 0.15 and 0.60 ± 0.13, DR: 1.24 ± 0.12 and 1.11 ± 0.10). Conclusions: Our results indicated that BCSFB function disturbances could be followed by Aβ accumulation, because the reduced interstitial flow preceded amyloid accumulation in the positive-change subjects, and amyloid accumulation was not observed in the older adults with sufficiently high values for the two indices. We believe that further elucidation of interstitial water flow will be the key to developing therapeutic strategies for AD, especially with regard to prevention.