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

Article type: Research Article

Authors: Ota, Miho^{a; b; *} | Sato, Noriko^a | Nakaya, Moto^{a; c} | Shigemoto, Yoko^a | Kimura, Yukio^a | Chiba, Emiko^a | Yokoi, Yuma^{d; e} | Tsukamoto, Tadashi^f | Matsuda, Hiroshi^{a; g}

Affiliations: [a] Department of Radiology, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan | [b] Department of Neuropsychiatry, University of Tsukuba, Tsukuba, Ibaraki, Japan | [c] Department of Radiology, Graduate School of Medicine, University of Tokyo Bunkyo-ku, Tokyo, Japan | [d] Department of Psychiatry, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan | [e] Department of Educational Promotion, Clinical Research & Education Promotion Division, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan | [f] Department of Neurology, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan | [g] Department of Biofunctional Imaging, Fukushima Medical University, Fukushima City, Fukushima, Japan

Correspondence: [*] Correspondence to: Dr. Miho Ota, Department of Radiology, National Center of Neurology and Psychiatry, 4-1-1, Ogawa-Higashi, Kodaira, Tokyo 187-8551, Japan. Tel.:+81 29 853 3182; E-mail: ota@md.tsukuba.ac.jp.

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

DOI: 10.3233/JAD-220534

Journal: Journal of Alzheimer's Disease, vol. 90, no. 1, pp. 295-303, 2022