Assessment of APOE in atypical parkinsonism syndromes

Marya S Sabir¹, Cornelis Blauwendraat¹, Sarah Ahmed¹, Geidy E Serrano², Thomas G Beach², Matthew Perkins³, Ann C Rice⁴, Eliezer Masliah⁵, Christopher M Morris⁶, Lasse Pihlstrom⁷, Alexander Pantelyat⁸, Susan M Resnick⁹, Mark R Cookson⁵, Dena G Hernandez⁵, Marilyn Albert⁸, Ted M Dawson¹⁰, Liana S Rosenthal⁸, Henry Houlden¹¹, Olga Pletnikova¹², Juan Troncoso¹², Sonja W Scholz¹³

Affiliations

¹ Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
² Civin Laboratory of Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USA.
³ Michigan Brain Bank, University of Michigan Medical School, Ann Arbor, MI, USA.
⁴ Virginia Commonwealth University Brain Bank, Virginia Commonwealth University, Richmond, VA, USA.
⁵ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
⁶ Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
⁷ Department of Neurology, Oslo University Hospital, Oslo, Norway.
⁸ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁹ Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
¹⁰ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Neuroregeneration and Stem Cell Programs, Institute of Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹ Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
¹² Department of Pathology (Neuropathology), Johns Hopkins University Medical Center, Baltimore, MD, USA.
¹³ Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: sonja.scholz@nih.gov.

PMID: 30798004
PMCID: PMC6588472
DOI: 10.1016/j.nbd.2019.02.016

Assessment of APOE in atypical parkinsonism syndromes

Marya S Sabir et al. Neurobiol Dis. 2019 Jul.

. 2019 Jul:127:142-146.

doi: 10.1016/j.nbd.2019.02.016. Epub 2019 Feb 21.

Authors

Affiliations

¹ Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
² Civin Laboratory of Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USA.
³ Michigan Brain Bank, University of Michigan Medical School, Ann Arbor, MI, USA.
⁴ Virginia Commonwealth University Brain Bank, Virginia Commonwealth University, Richmond, VA, USA.
⁵ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
⁶ Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
⁷ Department of Neurology, Oslo University Hospital, Oslo, Norway.
⁸ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁹ Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
¹⁰ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Neuroregeneration and Stem Cell Programs, Institute of Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹¹ Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
¹² Department of Pathology (Neuropathology), Johns Hopkins University Medical Center, Baltimore, MD, USA.
¹³ Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: sonja.scholz@nih.gov.

PMID: 30798004
PMCID: PMC6588472
DOI: 10.1016/j.nbd.2019.02.016

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.

Keywords: APOE; Atypical parkinsonism; Lewy body dementia; Multiple system atrophy; Progressive supranuclear palsy.

Published by Elsevier Inc.

PubMed Disclaimer

Conflict of interest statement

DISCLOSURE STATEMENT

The authors report no conflicts of interest.

References

1. World Health Organization. Neurological Disorders: Public Health Challenges. World Health Organization; 2006.
1. Scholz S, Bras J. Genetics Underlying Atypical Parkinsonism and Related Neurodegenerative Disorders. Int J Mol Sci. 2015;16(10):24629–24655. - PMC - PubMed
1. Irwin DJ, Cairns NJ, Grossman M, et al. Frontotemporal lobar degeneration: defining phenotypic diversity through personalized medicine. Acta Neuropathol. 2015;129(4):469–491. - PMC - PubMed
1. Spillantini MG, Goedert M. Synucleinopathies: past, present and future. Neuropathol Appl Neurobiol. 2016;42(1):3–5. - PubMed
1. Merdes AR, Hansen LA, Jeste DV, et al. Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies. Neurology. 2003;60(10):1586–1590. - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Consumer Health Information
- MedlinePlus Health Information
Research Materials
- Coriell Cell Repositories
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Assessment of APOE in atypical parkinsonism syndromes

Affiliations

Assessment of APOE in atypical parkinsonism syndromes

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous