Apo E genotypes in multiple sclerosis, Parkinson's disease, schwannomas and late-onset Alzheimer's disease

Rubinsztein, David C.; Hanlon, Charlotte; Irving, Richard; Goodburn, Sandy; Evans, D. Gareth; Kellar-Wood, H.; Xuereb, John H.; Bandmann, Oliver; Harding, A. E.

doi:10.1006/mcpr.1994.1073

Cited by 69 publications

(38 citation statements)

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“…These results are different from those reported for AD. 3 Low levels ofapo E occur in CSF ofMS patients but could result from decreased production of apo E, increased clearance of apo E from the neurofil, or local accumulation, as reported in the senile plaques of AD. 6 The lack of association ofa particular apo E genotype with MS may not suggest a genetically determined diminution of apo E secretion.…”

Section: Resultsmentioning

confidence: 90%

Apolipoprotein E Polymorphism in Multiple Sclerosis

et al. 1998

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Additional key phrases: apo E genotype; central nervous systemApolipoprotein E (apo E) is a polymorphic plasma protein involved in cholesterol transport. Apo E is produced and secreted in the central nervous system by astrocytes. Following peripheral nerve injury in rats, the synthesis of apo E increases 250-to 350-fold. A similar increase is observed in the central nervous system when the optic nerve and spinal cord are injured. It was suggested that apo E redistributes lipid, participates in cholesterol homeostasis in the brain and is implicated in the growth and repair of the nervous system. I Three common variants of apo E are present in the general human population, c2, d and fA coding for three isoforms (apo E2, apo E3, apo E4). These isoforms differ from each other by a single aminoacid substitution. The most frequent phenotype in the normal population is apo E3/ apo E3 and the two minor isoforms are associated with altered recognition of specific receptors. Recent genetic evidence suggests that inheritance of the c4 allele is associated with increased risk for sporadic and earlier onset of Alzheimer's disease (AD).2 In contrast, Rubinsztein found no influence of the apo E phenotype in a small group of patients with multiple sclerosis (MS).' MS is the major demyelinating disease. The increased higher incidence in women, the racial and familial clustering of MS cases and the high concordance rate in monozygotic twins (26%) compared with dizygotic twins (2'3%) and non twin siblings (1'9%), suggest that a genetic component influences susceptibility to MS. 4 We recently demonstrated that apo E concentrations in cerebrospinal fluid (CSF) and apo E intrathecal synthesis are decreased in MS patients. The reduction of CSF apo E levels may impair myelin repair and influence disease progression in MS patients.

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Section: Resultsmentioning

confidence: 90%

Apolipoprotein E Polymorphism in Multiple Sclerosis

et al. 1998

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“…In this disease it is likely that apo E4 is exerting a causal effect: apo E4 is associated with raised LDL-cholesterol levels (see above) and these are in turn associated with an increased predisposition to thrombosis. However, apo E genotypes do not seem to confer varying susceptibility risks in two other neurodegenerative diseases: Parkinson's disease and multiple sclerosis (Rubinsztein et al 1994).…”

Section: Apo E4: a Risk Factor For Alzheimer's Diseasementioning

confidence: 94%

Apolipoprotein E: a review of its roles in lipoprotein metabolism, neuronal growth and repair and as a risk factor for Alzheimer's disease

Rubinsztein¹

1995

Psychol. Med.

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“…Its ligand-receptor binding also activates various signal transductions (8)(9)(10). Therefore, it has been suggested that ApoE not only regulates lipid metabolism but also plays a key role in biological events such as nerve regeneration, antioxidant effects, immune response and cell proliferation (11)(12)(13). Moreover, concerning cancer field, ApoE has been correlated with cancer development in epithelial malignancies such as ovary or prostate (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%