Assessment of APOE in atypical parkinsonism syndromes.

Abstract

Atypical parkinsonism syndromes are a heterogeneous group of neurodegenerative disorders that include corticobasal degeneration (CBD), Lewy body dementia (LBD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). The APOE ε4 allele is a well-established risk factor for Alzheimer's disease; however, the role of APOE in atypical parkinsonism syndromes remains controversial. To examine the associations of APOE ε4 and ε2 alleles with risk of developing these syndromes, a total of 991 pathologically-confirmed atypical parkinsonism cases were genotyped using the Illumina NeuroChip array. We also performed genotyping and logistic regression analyses to examine APOE frequency and associated risk in patients with Alzheimer's disease (n = 571) and Parkinson's disease (n = 348). APOE genotypes were compared to those from neurologically healthy controls (n = 591). We demonstrate that APOE ε4 and ε2 carriers have a significantly increased and decreased risk, respectively, of developing Alzheimer's disease (ε4: OR: 4.13, 95% CI: 3.23-5.26, p = 3.67 × 10-30; ε2: OR: 0.21, 95% CI: 0.13-0.34; p = 5.39 × 10-10) and LBD (ε4: OR: 2.94, 95% CI: 2.34-3.71, p = 6.60 × 10-20; ε2: OR = OR: 0.39, 95% CI: 0.26-0.59; p = 6.88 × 10-6). No significant associations with risk for CBD, MSA, or PSP were observed. We also show that APOE ε4 decreases survival in a dose-dependent manner in Alzheimer's disease and LBD. Taken together, this study does not provide evidence to implicate a role of APOE in the neuropathogenesis of CBD, MSA, or PSP. However, we confirm association of the APOE ε4 allele with increased risk for LBD, and importantly demonstrate that APOE ε2 reduces risk of this disease.

• Authors: Marya S Sabir, Cornelis Blauwendraat, Sarah Ahmed, Geidy E Serrano, Thomas G Beach, Matthew Perkins, Ann C Rice, Eliezer Masliah, Christopher M Morris, Lasse Pihlstrom, Alexander Pantelyat, Susan M Resnick, Mark R Cookson, Dena G Hernandez, Marilyn Albert, Ted M Dawson, Liana S Rosenthal, Henry Houlden, Olga Pletnikova, Juan Troncoso, Sonja W Scholz
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 127 Pg. 142-146 (07 2019) ISSN: 1095-953X [Electronic] United States
• PMID: 30798004 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Published by Elsevier Inc.

Chemical References

• Apolipoproteins E

Topics

• Aged
• Aged, 80 and over
• Alleles
• Alzheimer Disease (genetics, pathology)
• Apolipoproteins E (genetics)
• Brain (pathology)
• Dementia (genetics, pathology)
• Female
• Genotype
• Humans
• Lewy Body Disease (genetics, pathology)
• Male
• Middle Aged
• Multiple System Atrophy (genetics, pathology)
• Parkinson Disease (genetics, pathology)
• Supranuclear Palsy, Progressive (genetics, pathology)