Assessment of APOE in atypical parkinsonism syndromes

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

Neurobiology of Disease (Jul 2019)

Assessment of APOE in atypical parkinsonism syndromes

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

Affiliations

Marya S. Sabir: Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
Cornelis Blauwendraat: Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
Sarah Ahmed: Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
Geidy E. Serrano: Civin Laboratory of Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USA
Thomas G. Beach: Civin Laboratory of Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USA
Matthew Perkins: Michigan Brain Bank, University of Michigan Medical School, Ann Arbor, MI, USA
Ann C. Rice: Virginia Commonwealth University Brain Bank, Virginia Commonwealth University, Richmond, VA, USA
Eliezer Masliah: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
Christopher M. Morris: Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
Lasse Pihlstrom: Department of Neurology, Oslo University Hospital, Oslo, Norway
Alexander Pantelyat: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Susan M. Resnick: Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
Mark R. Cookson: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
Dena G. Hernandez: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
Marilyn Albert: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Ted M. Dawson: 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
Liana S. Rosenthal: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Henry Houlden: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
Olga Pletnikova: Department of Pathology (Neuropathology), Johns Hopkins University Medical Center, Baltimore, MD, USA
Juan Troncoso: Department of Pathology (Neuropathology), Johns Hopkins University Medical Center, Baltimore, MD, USA
Sonja W. Scholz: 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; Corresponding author at: Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, Room 1A-215, Bethesda, MD 20892-3707, USA.

Journal volume & issue: Vol. 127
pp. 142 – 146

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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