| Anti-oxidative approach to prevent Alzheimer's type of dementia Koji Abe1; Haruhiko Inufusa2; Fuhua Yang3; Toshikazu Yoshikawa4; 1NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY, Tokyo, Japan; 2TIMA, Gifu, Japan; 3DIVISION OF ANTI-OXIDANT RESEARCH, GIFU UNIVERSITY, Gifu, Japan; 4LOUIS PASTEUR CENTER, Kyoto, Japan; PAPER: 423/Oxidative/Regular (Oral) SCHEDULED: 14:50/Wed. 30 Nov. 2022/Ballroom B ABSTRACT: Alzheimer's disease (AD) and chronic cerebral hypoperfusion (CCH) often coexist in dementia patients in aging societies. The hallmarks of AD including amyloid-β (Aβ)/phosphorylated tau (pTau) and pathology-related events such as neural oxidative stress and neuroinflammation play critical roles in pathogenesis of AD with CCH. A large number of lessons from failures of drugs targeting a single target or pathway on this so complicated disease indicate that disease-modifying therapies targeting multiple key pathways hold potent potential in therapy of the disease. In the present study, we used a novel mouse model of AD with CCH to investigate a potential therapeutic effect of a free radical scavenger, Edaravone (EDA) on AD with CCH via examining motor and cognitive capacity, AD hallmarks, neural oxidative stress, and neuroinflammation. Compared with AD with CCH mice at 12 months of age, EDA significantly improved motor and cognitive deficits, attenuated neuronal loss, reduced Aβ/pTau accumulation, and alleviated neural oxidative stress and neuroinflammation. These findings suggest that EDA possesses clinical and pathological benefits for AD with CCH in the present mouse model and has a potential as a therapeutic agent for AD with CCH via targeting multiple key pathways of the disease pathogenesis. In a clinical setting, anti-oxidative dietary supplement TwendeeX prevented cognitive function or even improved it with MMSE (minimental score examination) in mild cognitive impairment population. These results strongly suggest a promising function of anti-oxidative approach to prevent dementia. References: 1). Tadokoro K, Morihara R, Abe K, et al. Clinical Benefits of Antioxidative Supplement Twendee X for Mild Cognitive Impairment: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Prospective Interventional Study. J Alzheimers Dis. 2019; 71(3): 1063-1069.<br />2.) Feng T, Yamashita T, Abe K, et al. Clinical and Pathological Benefits of Edaravon for Alzheimar”s Disease with Chronic Cerebral Hypoperfusion in a Novel Mouse Model. J Alzheimars Dis. 2019; 71(1);327-339. <br />3). Feng T, Yamashita T, Abe K, et al. In Vitro Free Radical Scavenging Activities of Dietary Supplements by Electron Spin Resonance. Brain Supplements. 2020; 2: 1-12.<br />4). Tadokoro K, Ohta Y, Abe K, et al. Prevention of Cognitive Decline in Alzheimer’s Disease by Novel Sntioxidative Supplements. Int J Mol Sci. 2020 Mar 13:21(6) |
