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Neurology. 2010 May 18;74(20):1611-8. doi: 10.1212/WNL.0b013e3181e074a7.

APOE epsilon4 and the cognitive genetics of multiple sclerosis.

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  • 1Neuropsychiatry Program, Department of Psychiatry, Sunnybrook Health Sciences Centre, FG08-2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.



Evidence linking APOE to myelin repair, neuronal plasticity, and cerebral inflammatory processes suggests that it may be relevant in multiple sclerosis (MS). The purpose of this study was to determine whether the epsilon4 allele of APOE is associated with cognitive deficits in patients with MS.


Using a case-control design, 50 patients with MS with the epsilon4 allele (epsilon4+) and 50 epsilon4-negative (epsilon4-) patients with MS were tested using a comprehensive battery of tests evaluating the cognitive domains most often affected in MS.


The epsilon4+ and epsilon4- patients with MS were well-matched with respect to demographic variables (age, gender, ethnicity, education, employment status, premorbid IQ) and disease variables (disease course, disease duration, Expanded Disability Status Scale, 25-foot timed walk, 9-hole pegboard test). In addition, the groups were similar in depressive symptoms, in the proportion of patients receiving disease-modifying therapy, and in carriage of the APOE epsilon2 allele. Results showed that none of the 11 cognitive outcome variables differed between epsilon4+ and epsilon4- patients with MS. Cognitive measures were also unrelated to epsilon4 interactions with age and gender. The incidence of overall cognitive dysfunction did not differ between epsilon4+ and epsilon4- groups, nor did failure on any test, and epsilon4 carriage was not a significant predictor of any adverse cognitive outcome. These negative results endured with the exclusion of epsilon2+ subjects from the analyses.


This study does not support a role for the epsilon4 allele in cognitive dysfunction in multiple sclerosis.

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