Affiliations: [a] Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Perth, WA, Australia | [b] School of Pharmacology and Medicine, University of Western Australia, Perth, WA, Australia | [c] Centre for Clinical Research in Neuropsychiatry, Graylands Hospital, University of Western Australia, Perth, WA, Australia | [d] McCusker Foundation for Alzheimer's Disease Research, Hollywood Private Hospital, Perth, WA, Australia | [e] School of Psychiatry and Clinical Neuroscience, University of Western Australia, Perth, WA, Australia
Correspondence:
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Correspondence to: Professor Ralph N. Martins, Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, WA, Australia. Tel.: +61 8 6304 5456; Fax: +61 8 6304 5851; E-mail: r.martins@ecu.edu.au.
Abstract: The E4 allele of the apolipoprotein E (ApoE) gene has been identified as a major risk factor for the development of late onset Alzheimer's disease (AD). However, the mechanisms by which this gene affects AD are not fully understood. Studies of ApoE knock-out (ApoE KO) mice have revealed an exacerbation of two major pathologies that are diagnostic of AD: neurofibrillary tangles and senile plaques. However, evidence as to whether these mice have cognitive deficits is not yet conclusive. This ambiguity may arise partly from confounds associated with reliance on limited memory models, primarily, the Morris water maze task. An 8-arm radial maze task was therefore used to measure spatial memory in the ApoE KO mice, compared to controls over time. Furthermore, the effectiveness of a combination antioxidant therapy (CAT), designed to slow down the progression of AD based on concepts of oxidative stress and inflammatory processes underlying the pathology, was tested on memory ability. A significant strain difference was observed with the ApoE KO mice performing better than controls in terms of reference memory and corrects entries. No significant strain difference was observed for performance in terms of working memory errors. No significant effect of the CAT supplementation was observed.
