Antroquinonol administration in animal preclinical studies for Alzheimer's disease (AD): A new avenue for modifying progression of AD pathophysiology

Despite the rise of Alzheimer's disease (AD) in an ageing population, no cure is currently available for this dis-order. This study assessed the role of a natural compound, Antroquinonol, in modifying the progression of AD when administered at the start and/or before appearance of symptoms and when the disease was well established, in a transgenic animal model. Antroquinonol was administered daily for 8 weeks, in 11 week (early stage) and 9 month (late stage) male transgenic mice (3 times Transgenic mice PS1M146V, APPSwe, and tauP301L, 3 Tg XAD) and their respective aged controls. Behavioural testing (including Elevated Plus Maze Watermaze, Recognition object testing and Y maze) was performed at the end of the drug administration. In addition AD biomarkers (Amyloid beta 42 (A beta 42), tau and phospho-tau levels), oxidative stress and inflammatory markers, were assessed in tested mice brains after their sacrifice at the end of the treatment. When administered before the start of symptoms at 11 weeks, Antroquinonol treatment at 34 mg/kg (D2) and more consistently at 75 mg/kg (D3), had a significant effect on reducing systemic inflammatory markers (Interleukin 1, IL-1 beta and TNF-alpha) and AD biomarker (Amyloid Beta 42, A beta 42 and tau) levels in the brain. The reduction of behavioural impairment reported for 3TgXAD mice was observed significantly for the D3 drug dose only and for all behavioural tests, when administered at 11 weeks.Similarly, beneficial effects of Antroquinonol (at higher dose D3) were noted in the transgenic mice in terms of AD biomarkers (tau and phosphorylated-tau), systemic inflammatory (IL-1 beta), brain anti-inflammatory (Nrf2) and oxidative (3-Nitrotyrosine, 3NT) markers. Improvement of memory impairment was also reported when Antro-quinonol (D3) was administered at late stage (9 months). Since Antroquinonol has been used without adverse effects in previous successful clinical trials, this drug may offer a new avenue of treatment to modify AD development and progression.