Abstract
Epidemiological studies provide strong evidence that susceptibility to multiple sclerosis
(MS) is in part genetically determined. Likewise the heterogeneity in clinical manifestations,
temporal course, severity, and in the pathological processes of MS are probably also
influenced by our genes. Apolipoprotein E (apoE) polymorphism has been considered
a candidate for impacting on MS because of its numerous functions related to brain
tissue and evidence for an association with a variety of cerebral disorders, specifically
Alzheimer's disease (AD). The apoE alleles ε2, ε3, and ε4 are known to impact differently
on aspects such as neuronal growth and repair, neuroprotection and inflammation. After
a review of the strong association of the apoE polymorphism with AD, we review the
results on MS. These are far less homogenous but have gained support from morphologic
and metabolic measures obtained with magnetic resonance imaging indicating a greater
extent of brain destruction with the apoE ε4 allele. Evidence for a protective role
of the ε2 allele in MS is weak. In view of the association with AD it is tempting
to speculate that neuropsychologic functioning in MS might be even more strongly related
to the apoE polymorphism and especially to the ε4 allele than other deficits, but
few data on this issue are yet available. While part of the association of the apoE
polymorphism with AD is supposed to be caused by apoE-isoform dependent effects on
amyloid-beta deposition, no single pathogenetically relevant mechanism has yet been
confirmed for MS. In summary we presently may assume only subtle effects of the apoE
polymorphism on the course of MS. These effects are probably further modulated by
other genes and need further investigation.
Keywords
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Article info
Publication history
Accepted:
August 10,
2005
Received in revised form:
July 11,
2005
Received:
February 26,
2005
Identification
Copyright
© 2006 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
