Abstract | OBJECTIVES: To determine if apolipoprotein E epsilon 4 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 epsilon 4 to Alzheimer-type pathologic features was determined. RESULTS: Across all neurodegenerative disorders, apolipoprotein E epsilon 4 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 epsilon 4 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 epsilon 4 allele was not significantly different among the 3 groups. CONCLUSIONS:
Apolipoprotein E epsilon 4, 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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Authors | Keith A Josephs, Yoshio Tsuboi, Natalie Cookson, Hilary Watt, Dennis W Dickson |
Journal | Archives of neurology
(Arch Neurol)
Vol. 61
Issue 10
Pg. 1579-84
(Oct 2004)
ISSN: 0003-9942 [Print] United States |
PMID | 15477512
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Apolipoprotein E4
- Apolipoproteins E
- Genetic Markers
- Nerve Tissue Proteins
- Synucleins
- tau Proteins
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Topics |
- Aged
- Aged, 80 and over
- Alzheimer Disease
(complications, genetics, pathology)
- Apolipoprotein E4
- Apolipoproteins E
(genetics)
- Dementia
(etiology, pathology)
- Female
- Genetic Markers
(genetics)
- Humans
- Male
- Nerve Tissue Proteins
(genetics)
- Neurofibrillary Tangles
(pathology)
- Odds Ratio
- Plaque, Amyloid
(pathology)
- Sex Factors
- Synucleins
- Tauopathies
(etiology, pathology)
- tau Proteins
(genetics)
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