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 Isa Shapiro Rosenthal, Henry Houlden, Olga Pletnikova, Juan C TroncosoSonja W. Scholz

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)142-146
Number of pages5
JournalNeurobiology of Disease
Volume127
DOIs
StatePublished - Jul 1 2019

Fingerprint

Parkinsonian Disorders
Lewy Body Disease
Progressive Supranuclear Palsy
Multiple System Atrophy
Alzheimer Disease
Alleles
Neurodegenerative Diseases
Parkinson Disease
Logistic Models
Genotype
Regression Analysis
Survival

Keywords

  • APOE
  • Atypical parkinsonism
  • Lewy body dementia
  • Multiple system atrophy
  • Progressive supranuclear palsy

ASJC Scopus subject areas

  • Neurology

Cite this

Sabir, M. S., Blauwendraat, C., Ahmed, S., Serrano, G. E., Beach, T. G., Perkins, M., ... Scholz, S. W. (2019). Assessment of APOE in atypical parkinsonism syndromes. Neurobiology of Disease, 127, 142-146. https://doi.org/10.1016/j.nbd.2019.02.016

Assessment of APOE in atypical parkinsonism syndromes. / Sabir, Marya S.; Blauwendraat, Cornelis; Ahmed, Sarah; Serrano, Geidy E.; Beach, Thomas G.; Perkins, Matthew; Rice, Ann C.; Masliah, Eliezer; Morris, Christopher M.; Pihlstrom, Lasse; Pantelyat, Alexander; Resnick, Susan M.; Cookson, Mark R.; Hernandez, Dena G.; Albert, Marilyn; Dawson, Ted M; Rosenthal, Liana Isa Shapiro; Houlden, Henry; Pletnikova, Olga; Troncoso, Juan C; Scholz, Sonja W.

In: Neurobiology of Disease, Vol. 127, 01.07.2019, p. 142-146.

Research output: Contribution to journalArticle

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, LIS, Houlden, H, Pletnikova, O, Troncoso, JC & Scholz, SW 2019, 'Assessment of APOE in atypical parkinsonism syndromes', Neurobiology of Disease, vol. 127, pp. 142-146. https://doi.org/10.1016/j.nbd.2019.02.016
Sabir MS, Blauwendraat C, Ahmed S, Serrano GE, Beach TG, Perkins M et al. Assessment of APOE in atypical parkinsonism syndromes. Neurobiology of Disease. 2019 Jul 1;127:142-146. https://doi.org/10.1016/j.nbd.2019.02.016
Sabir, Marya S. ; Blauwendraat, Cornelis ; Ahmed, Sarah ; Serrano, Geidy E. ; Beach, Thomas G. ; Perkins, Matthew ; Rice, Ann C. ; Masliah, Eliezer ; Morris, Christopher M. ; Pihlstrom, Lasse ; Pantelyat, Alexander ; Resnick, Susan M. ; Cookson, Mark R. ; Hernandez, Dena G. ; Albert, Marilyn ; Dawson, Ted M ; Rosenthal, Liana Isa Shapiro ; Houlden, Henry ; Pletnikova, Olga ; Troncoso, Juan C ; Scholz, Sonja W. / Assessment of APOE in atypical parkinsonism syndromes. In: Neurobiology of Disease. 2019 ; Vol. 127. pp. 142-146.
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AU - Blauwendraat, Cornelis

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AU - Beach, Thomas G.

AU - Perkins, Matthew

AU - Rice, Ann C.

AU - Masliah, Eliezer

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AU - Hernandez, Dena G.

AU - Albert, Marilyn

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AU - Troncoso, Juan C

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N2 - 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.

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