TY - JOUR
T1 - Assessment of APOE in atypical parkinsonism syndromes
AU - Sabir, Marya S.
AU - Blauwendraat, Cornelis
AU - Ahmed, Sarah
AU - Serrano, Geidy E.
AU - Beach, Thomas G.
AU - Perkins, Matthew
AU - Rice, Ann C.
AU - Masliah, Eliezer
AU - Morris, Christopher M.
AU - Pihlstrom, Lasse
AU - Pantelyat, Alexander
AU - Resnick, Susan M.
AU - Cookson, Mark R.
AU - Hernandez, Dena G.
AU - Albert, Marilyn
AU - Dawson, Ted M.
AU - Rosenthal, Liana S.
AU - Houlden, Henry
AU - Pletnikova, Olga
AU - Troncoso, Juan
AU - Scholz, Sonja W.
N1 - Publisher Copyright:
© 2019
PY - 2019/7
Y1 - 2019/7
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.
AB - 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.
KW - APOE
KW - Atypical parkinsonism
KW - Lewy body dementia
KW - Multiple system atrophy
KW - Progressive supranuclear palsy
UR - http://www.scopus.com/inward/record.url?scp=85062424189&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062424189&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2019.02.016
DO - 10.1016/j.nbd.2019.02.016
M3 - Article
C2 - 30798004
AN - SCOPUS:85062424189
SN - 0969-9961
VL - 127
SP - 142
EP - 146
JO - Neurobiology of Disease
JF - Neurobiology of Disease
ER -