Toggle Main Menu Toggle Search

Open Access padlockePrints

Assessment of APOE in atypical parkinsonism syndromes

Lookup NU author(s): Dr Christopher Morris

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

© 2019 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.


Publication metadata

Author(s): Sabir MS, Blauwendraat C, Ahmed S, Serrano GE, Beach TG, Perkins M, Rice AC, Masliah E, Morris CM, Pihlstrom L, Pantelyat A, Resnick SM, Cookson MR, Hernandez DG, Albert M, Dawson TM, Rosenthal LS, Houlden H, Pletnikova O, Troncoso J, Scholz SW

Publication type: Article

Publication status: Published

Journal: Neurobiology of Disease

Year: 2019

Volume: 127

Pages: 142-146

Print publication date: 01/07/2019

Online publication date: 21/02/2019

Acceptance date: 20/02/2019

ISSN (print): 0969-9961

ISSN (electronic): 1095-953X

Publisher: Academic Press Inc.

URL: https://doi.org/10.1016/j.nbd.2019.02.016

DOI: 10.1016/j.nbd.2019.02.016


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share