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

Journal article


Fernandez, Francesca, Aust, Caitlin, Lye, Sarah and Griffiths, Lyn. (2022). Antroquinonol administration in animal preclinical studies for Alzheimer's disease (AD) : A new avenue for modifying progression of AD pathophysiology. Brain, Behavior, and Immunity. 21, p. Article 100435. https://doi.org/10.1016/j.bbih.2022.100435
AuthorsFernandez, Francesca, Aust, Caitlin, Lye, Sarah and Griffiths, Lyn
Abstract

Despite the rise of Alzheimer's disease (AD) in an ageing population, no cure is currently available for this disorder. 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 (Aβ42), 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-1β and TNF-α) and AD biomarker (Amyloid Beta 42, Aβ42 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-1β), brain anti-inflammatory (Nrf2) and oxidative (3-Nitrotyrosine, 3NT) markers. Improvement of memory impairment was also reported when Antroquinonol (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.

KeywordsAlzheimer's disease (AD); animal model of AD; transgenic mice; AD biomarkers; inflammatory markers; antroquinonol; behavioural testing
Year2022
JournalBrain, Behavior, and Immunity
Journal citation21, p. Article 100435
PublisherElsevier Inc.
ISSN0889-1591
Digital Object Identifier (DOI)https://doi.org/10.1016/j.bbih.2022.100435
Open accessPublished as ‘gold’ (paid) open access
Research or scholarlyResearch
Page range1-10
Publisher's version
License
File Access Level
Open
Output statusPublished
Publication dates
Online24 Feb 2022
Publication process dates
Accepted22 Feb 2022
Deposited09 Jun 2022
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