Apolipoprotein e ε4 is a determinant for Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration

Keith Anthony Josephs, Yoshio Tsuboi, Natalie Cookson, Hilary Watt, Dennis W Dickson

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Objectives: To determine if apolipoprotein E ε4 influences the frequency of Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration and to determine if the frequency of Alzheimer-type pathologic features in synucleinopathies is similar to the frequency of such features in tauopathies and frontotemporal degeneration. Methods: A total of 285 patients with pathologically proven neurodegenerative disorders, including diffuse and transitional Lewy body disease, frontotemporal degeneration, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy, with a mean age of 75.1 ± 9.3 years, were suitable for genetic and pathological analysis. Disorders were grouped as tauopathies (progressive supranuclear palsy and corticobasal degeneration), synucleinopathies (Lewy body disease and multiple system atrophy), and frontotemporal degeneration. Braak neurofibrillary tangle staging and quantitative scores of senile plaques were used to determine the degree of concomitant Alzheimer-type pathologic features in each case, and apolipoprotein E genotype was determined from DNA isolated from frozen brain tissue. The relationship of apolipoprotein E ε4 to Alzheimer-type pathologic features was determined. Results: Across all neurodegenerative disorders, apolipoprotein E ε4 and older age independently predicted the co-occurrence of Alzheimer-type pathologic features (P<.001), whereas female sex had a lesser effect (P = .03). When divided into the 3 subgroups (tauopathies, synucleinopathies, and frontotemporal degeneration), apolipoprotein E ε4 had a similar effect, whereas older age and female sex were less predictive. There was a significant difference between the frequency of Alzheimer-type pathologic features in synucleinopathies and the frequency of such features in tauopathies and frontotemporal degeneration (P<.001 for both). The frequency of apolipoprotein E ε4 allele was not significantly different among the 3 groups. Conclusions: Apolipoprotein E ε4, independent of older age and sex, contributes to the co-occurrence of Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration, but this does not explain why Alzheimer-type pathologic features are significantly more likely to coexist with synucleinopathies than with either tauopathies or frontotemporal degeneration.

Original languageEnglish (US)
Pages (from-to)1579-1584
Number of pages6
JournalArchives of Neurology
Volume61
Issue number10
DOIs
StatePublished - Oct 2004

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Tauopathies
Apolipoprotein E4
Apolipoproteins
Progressive Supranuclear Palsy
Multiple System Atrophy
Lewy Body Disease
Neurodegenerative Diseases
Neurofibrillary Tangles
Amyloid Plaques
Apolipoproteins E
Alzheimer
Degeneration
Alleles
Genotype
DNA
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Apolipoprotein e ε4 is a determinant for Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration. / Josephs, Keith Anthony; Tsuboi, Yoshio; Cookson, Natalie; Watt, Hilary; Dickson, Dennis W.

In: Archives of Neurology, Vol. 61, No. 10, 10.2004, p. 1579-1584.

Research output: Contribution to journalArticle

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title = "Apolipoprotein e ε4 is a determinant for Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration",
abstract = "Objectives: To determine if apolipoprotein E ε4 influences the frequency of Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration and to determine if the frequency of Alzheimer-type pathologic features in synucleinopathies is similar to the frequency of such features in tauopathies and frontotemporal degeneration. Methods: A total of 285 patients with pathologically proven neurodegenerative disorders, including diffuse and transitional Lewy body disease, frontotemporal degeneration, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy, with a mean age of 75.1 ± 9.3 years, were suitable for genetic and pathological analysis. Disorders were grouped as tauopathies (progressive supranuclear palsy and corticobasal degeneration), synucleinopathies (Lewy body disease and multiple system atrophy), and frontotemporal degeneration. Braak neurofibrillary tangle staging and quantitative scores of senile plaques were used to determine the degree of concomitant Alzheimer-type pathologic features in each case, and apolipoprotein E genotype was determined from DNA isolated from frozen brain tissue. The relationship of apolipoprotein E ε4 to Alzheimer-type pathologic features was determined. Results: Across all neurodegenerative disorders, apolipoprotein E ε4 and older age independently predicted the co-occurrence of Alzheimer-type pathologic features (P<.001), whereas female sex had a lesser effect (P = .03). When divided into the 3 subgroups (tauopathies, synucleinopathies, and frontotemporal degeneration), apolipoprotein E ε4 had a similar effect, whereas older age and female sex were less predictive. There was a significant difference between the frequency of Alzheimer-type pathologic features in synucleinopathies and the frequency of such features in tauopathies and frontotemporal degeneration (P<.001 for both). The frequency of apolipoprotein E ε4 allele was not significantly different among the 3 groups. Conclusions: Apolipoprotein E ε4, independent of older age and sex, contributes to the co-occurrence of Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration, but this does not explain why Alzheimer-type pathologic features are significantly more likely to coexist with synucleinopathies than with either tauopathies or frontotemporal degeneration.",
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T1 - Apolipoprotein e ε4 is a determinant for Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration

AU - Josephs, Keith Anthony

AU - Tsuboi, Yoshio

AU - Cookson, Natalie

AU - Watt, Hilary

AU - Dickson, Dennis W

PY - 2004/10

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N2 - Objectives: To determine if apolipoprotein E ε4 influences the frequency of Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration and to determine if the frequency of Alzheimer-type pathologic features in synucleinopathies is similar to the frequency of such features in tauopathies and frontotemporal degeneration. Methods: A total of 285 patients with pathologically proven neurodegenerative disorders, including diffuse and transitional Lewy body disease, frontotemporal degeneration, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy, with a mean age of 75.1 ± 9.3 years, were suitable for genetic and pathological analysis. Disorders were grouped as tauopathies (progressive supranuclear palsy and corticobasal degeneration), synucleinopathies (Lewy body disease and multiple system atrophy), and frontotemporal degeneration. Braak neurofibrillary tangle staging and quantitative scores of senile plaques were used to determine the degree of concomitant Alzheimer-type pathologic features in each case, and apolipoprotein E genotype was determined from DNA isolated from frozen brain tissue. The relationship of apolipoprotein E ε4 to Alzheimer-type pathologic features was determined. Results: Across all neurodegenerative disorders, apolipoprotein E ε4 and older age independently predicted the co-occurrence of Alzheimer-type pathologic features (P<.001), whereas female sex had a lesser effect (P = .03). When divided into the 3 subgroups (tauopathies, synucleinopathies, and frontotemporal degeneration), apolipoprotein E ε4 had a similar effect, whereas older age and female sex were less predictive. There was a significant difference between the frequency of Alzheimer-type pathologic features in synucleinopathies and the frequency of such features in tauopathies and frontotemporal degeneration (P<.001 for both). The frequency of apolipoprotein E ε4 allele was not significantly different among the 3 groups. Conclusions: Apolipoprotein E ε4, independent of older age and sex, contributes to the co-occurrence of Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration, but this does not explain why Alzheimer-type pathologic features are significantly more likely to coexist with synucleinopathies than with either tauopathies or frontotemporal degeneration.

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