Assessment of APOE in atypical parkinsonism syndromes
| Autor: | Thomas G. Beach, Mark R. Cookson, Dena G. Hernandez, Juan C. Troncoso, Eliezer Masliah, Lasse Pihlstrøm, Susan M. Resnick, Liana S. Rosenthal, Matthew H. Perkins, Olga Pletnikova, Alexander Pantelyat, Ted M. Dawson, Sarah A. Ahmed, Geidy E. Serrano, Marya S. Sabir, Marilyn S. Albert, Cornelis Blauwendraat, Henry Houlden, Ann C. Rice, Christopher Morris, Sonja W. Scholz |
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| Rok vydání: | 2019 |
| Předmět: |
Lewy Body Disease
Male 0301 basic medicine Oncology Apolipoprotein E medicine.medical_specialty Genotype Disease Article lcsh:RC321-571 Progressive supranuclear palsy 03 medical and health sciences Apolipoproteins E 0302 clinical medicine Atrophy Alzheimer Disease Internal medicine medicine Humans Corticobasal degeneration Dementia Risk factor lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Alleles Aged Aged 80 and over Lewy body business.industry Brain Parkinson Disease Multiple system atrophy Middle Aged medicine.disease 030104 developmental biology Atypical parkinsonism Neurology Female Supranuclear Palsy Progressive Lewy body dementia business APOE 030217 neurology & neurosurgery |
| Zdroj: | Neurobiology of Disease, Vol 127, Iss, Pp 142-146 (2019) Neurobiol Dis |
| ISSN: | 0969-9961 |
| DOI: | 10.1016/j.nbd.2019.02.016 |
| Popis: | 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 e4 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 e4 and e2 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 e4 and e2 carriers have a significantly increased and decreased risk, respectively, of developing Alzheimer's disease (e4: OR: 4.13, 95% CI: 3.23–5.26, p = 3.67 × 10−30; e2: OR: 0.21, 95% CI: 0.13–0.34; p = 5.39 × 10−10) and LBD (e4: OR: 2.94, 95% CI: 2.34–3.71, p = 6.60 × 10−20; e2: 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 e4 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 e4 allele with increased risk for LBD, and importantly demonstrate that APOE e2 reduces risk of this disease. |
| Databáze: | OpenAIRE |
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