Assessment of APOE in atypical parkinsonism syndromes

NEUROBIOLOGY OF DISEASE

卷:127

Article

Sabir, Marya S.¹  Blauwendraat, Cornelis¹  Ahmed, Sarah¹  Serrano, Geidy E.²  Beach, Thomas G.²  Perkins, Matthew³  Rice, Ann C.⁴  Masliah, Eliezer⁵  Morris, Christopher M.⁶  Pihlstrom, Lasse⁷  Pantelyat, Alexander⁸  Resnic, Susan M.⁹  Cookson, Mark R.⁵  Hernandez, Dena G.⁵  Albert, Marilyn⁸  Dawson, Ted M.^8,10,11,12  Rosenthal, Liana S.⁸  Houlden, Henry¹³  Pletnikova, Olga¹⁴  Troncoso, Juan¹⁴  Scholz, Sonja W.^1,8 

[1] NINDS, Neurodegenerat Dis Res Unit, NIH, 35 Convent Dr,Room 1A-215, Bethesda, MD 20892 USA

[2] Banner Sun Hlth Res Inst, Civin Lab Neuropathol, Sun City, AZ USA

[3] Univ Michigan, Sch Med, Michigan Brain Bank, Ann Arbor, MI USA

[4] Virginia Commonwealth Univ, Virginia Commonwealth Univ Brain Bank, Richmond, VA USA

[5] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

[6] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne, Tyne & Wear, England

[7] Oslo Univ Hosp, Dept Neurol, Oslo, Norway

[8] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[9] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA

[10] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Neuroregenerat & Stem Cell Programs, Baltimore, MD USA

[11] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[12] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD USA

[13] UCL Inst Neurol, Dept Mol Neurosci, London, England

[14] Johns Hopkins Univ, Med Ctr, Dept Pathol Neuropathol, Baltimore, MD 21218 USA

关键词: APOE;    Atypical parkinsonism;    Lewy body dementia;    Progressive supranuclear palsy;    Multiple system atrophy;   

DOI  :  10.1016/j.nbd.2019.02.016

来源: Elsevier

【 摘 要 】

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 epsilon 4 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 epsilon 4 and epsilon 2 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 epsilon 4 and epsilon 2 carriers have a significantly increased and decreased risk, respectively, of developing Alzheimer's disease (epsilon 4: OR: 4.13, 95% CI: 3.23-5.26, p = 3.67 x 10(-30); epsilon 2: OR: 0.21, 95% CI: 0.13-0.34; p = 5.39 x 10(-10)) and LBD (epsilon 4: OR: 2.94, 95% CI: 2.34-3.71, p = 6.60 x 10(-20); epsilon 2: OR = OR: 0.39, 95% CI: 0.26-0.59; p = 6.88 x 10(-6)). No significant associations with risk for CBD, MSA, or PSP were observed. We also show that APOE epsilon 4 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 epsilon 4 allele with increased risk for LBD, and importantly demonstrate that APOE epsilon 2 reduces risk of this disease.

【 授权许可】

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