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Neurobiol Dis. 2019 Feb 21;127:142-146. doi: 10.1016/j.nbd.2019.02.016. [Epub ahead of print]

Assessment of APOE in atypical parkinsonism syndromes.

Author information

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.

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

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

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