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Apolipoprotein E epsilon 4 is a determinant for Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration.
Arch Neurol. 2004 Oct; 61(10):1579-84.AN

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.

Authors+Show Affiliations

Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA. josephs.keith@mayo.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15477512

Citation

Josephs, Keith A., et al. "Apolipoprotein E Epsilon 4 Is a Determinant for Alzheimer-type Pathologic Features in Tauopathies, Synucleinopathies, and Frontotemporal Degeneration." Archives of Neurology, vol. 61, no. 10, 2004, pp. 1579-84.
Josephs KA, Tsuboi Y, Cookson N, et al. Apolipoprotein E epsilon 4 is a determinant for Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration. Arch Neurol. 2004;61(10):1579-84.
Josephs, K. A., Tsuboi, Y., Cookson, N., Watt, H., & Dickson, D. W. (2004). Apolipoprotein E epsilon 4 is a determinant for Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration. Archives of Neurology, 61(10), 1579-84.
Josephs KA, et al. Apolipoprotein E Epsilon 4 Is a Determinant for Alzheimer-type Pathologic Features in Tauopathies, Synucleinopathies, and Frontotemporal Degeneration. Arch Neurol. 2004;61(10):1579-84. PubMed PMID: 15477512.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Apolipoprotein E epsilon 4 is a determinant for Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration. AU - Josephs,Keith A, AU - Tsuboi,Yoshio, AU - Cookson,Natalie, AU - Watt,Hilary, AU - Dickson,Dennis W, PY - 2004/10/13/pubmed PY - 2004/12/16/medline PY - 2004/10/13/entrez SP - 1579 EP - 84 JF - Archives of neurology JO - Arch. Neurol. VL - 61 IS - 10 N2 - 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. SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/15477512/Apolipoprotein_E_epsilon_4_is_a_determinant_for_Alzheimer_type_pathologic_features_in_tauopathies_synucleinopathies_and_frontotemporal_degeneration_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneur.61.10.1579 DB - PRIME DP - Unbound Medicine ER -