Relationships Between the Deposition of Amyloid-β and Tau Protein and Glymphatic System Activity in Alzheimer's Disease: Diffusion Tensor Image Study

J Alzheimers Dis. 2022;90(1):295-303. doi: 10.3233/JAD-220534.

Abstract

Background: Amyloid-β (Aβ) and tau protein accumulation in the brain is thought to be one of the causes of Alzheimer's disease (AD). Recent study found that the glymphatic system was waste drainage system in the brain and promoting the elimination of Aβ and tau protein.

Objective: We evaluated the relationships between the glymphatic system activity and the Aβ and tau protein deposition.

Methods: Subjects were 21 patients with AD and 36 healthy subjects who underwent diffusion tensor imaging (DTI) scan and the positron emission tomography (PET) using with the Aβ tracer: 11C-PiB and the tau/inflammatory tracer: 18F-THK5351. We computed diffusion tensor image analysis along the perivascular space (DTI-ALPS) index as the proxy of glymphatic system activity, and estimated the relationships between the DTI-ALPS index and Aβ and tau protein/inflammatory deposition.

Results: We found significant negative correlations between DTI-ALPS index and the standard uptake value ratio (SUVR) of 11C-PiB in the bilateral temporal and left parietal cortices and left posterior cingulate gyrus in all subjects. Further, we detected significant negative correlations between DTI-ALPS index and the SUVR of 18F-THK5351 in the bilateral temporal cortices and right parietal cortex in all participants, too.

Conclusion: Our data suggested that DTI-ALPS index was a good biomarker for the evaluation of Aβ and tau deposition and neuroinflammation, and this marker might be effective to estimate the glymphatic system activity.

Keywords: 11C-PiB; 18F-THK5351; Diffusion tensor image analysis along the perivascular space (DTI-ALPS); positron emission tomography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Diffusion Tensor Imaging / methods
  • Glymphatic System* / diagnostic imaging
  • Glymphatic System* / metabolism
  • Humans
  • Positron-Emission Tomography / methods
  • tau Proteins / metabolism

Substances

  • tau Proteins
  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • THK5351
  • Amyloid beta-Peptides