Apolipoprotein E in Guamanian amyotrophic lateral sclerosis/parkinsonism-dementia complex: Genotype analysis and relationships to neuropathological changes

Luc Buée, Jordi Pérez-Tur, Béatrice Leveugle, Valérie Buée-Scherrer, Elliott J. Mufson, Arthur J. Loerzel, Marie Christine Chartier-Harlin, Daniel P. Perl, André Delacourte, Patrick R. Hof

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17 Scopus citations

Abstract

Apolipoprotein E (Apo E) has been recently identified within amyloid deposits and neurofibrillary tangles in the brains of Alzheimer's disease (AD) patients. A strong association of the Apo E ε4 allele with higher risk of developing AD has also been reported. In the present study, the distribution of Apo E and the possible relationship between Apo E alleles and neuropathological alterations were analyzed in a series of Guamanian amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) cases, a neurodegenerative condition characterized neuropathologically by widespread, severe neurofibrillary tangle formation but rare amyloid deposits. ApoE immunoreactivity was consistently observed in both type of lesions in these cases. Compared to tau protein immunoreactivity, there were generally fewer Apo E-immunoreactive neurofibrillary tangles, particularly in the deep layers of the neocortex and in the hippocampus. Genotype analysis revealed that the ε4 allele frequency was 5.9%, the ε3 allele frequency 88.2%, and the ε2 allele frequency 5.9% in this series. Recent data suggest that the Apo E4 variant may induce amyloidogenesis, while E2 could have a neuroprotective role. However, the rare Guamanian patients with amyloid deposits in cortical areas were not related to the ε4 allele, since all cases with senile plaques were ε3/ε3. In addition, compared to unaffected Guamanian cases and other Asian-Pacific populations previously reported, the observed low frequency of the ε2 allele in the present cases, which may be consistent with the notion that this allele, may represent a neuroprotective factor in several neurodegenerative disorders. The present data indicate that there is a strong interaction between Apo E deposition and neurofibrillary changes in Guamanian ALS-PDC.

Original languageEnglish
Pages (from-to)247-253
Number of pages7
JournalActa Neuropathologica
Volume91
Issue number3
DOIs
StatePublished - 1996

Keywords

  • Amyotrophic lateral sclerosis
  • Apolipoprotein E
  • Guam
  • Parkinsonism-dementia
  • Tau proteins

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