Examination of the Effect of Rare Variants in TREM2, ABI3, and PLCG2 in LOAD Through Multiple Phenotypes.
J Alzheimers Dis
; 77(4): 1469-1482, 2020.
Article
em En
| MEDLINE
| ID: mdl-32894242
ABSTRACT
BACKGROUND:
Rare variants in PLCG2 (p.P522R), ABI3 (p.S209F), and TREM2 (p.R47H, p.R62H) have been associated with late onset Alzheimer's disease (LOAD) risk in Caucasians. After the initial report, several studies have found positive results in cohorts of different ethnic background and with different phenotype.OBJECTIVE:
In this study, we aim to evaluate the association of rare coding variants in PLCG2, ABI3, and TREM2 with LOAD risk and their effect at different time points of the disease.METHODS:
We used a European American cohort to assess the association of the variants prior onset (using CSF Aß42, tau, and pTau levels, and amyloid imaging as endophenotypes) and after onset (measured as rate of memory decline).RESULTS:
We confirm the association with LOAD risk of TREM2 p.R47H, p.R62H and ABI3 p.S209F variants, and the protective effect of PLCG2 p.P522R. In addition, ABI3 and TREM2 gene-sets showed significant association with LOAD risk. TREM2 p.R47H and PLCG2 p.P522R variants were also statistically associated with increase of amyloid imaging and AD progression, respectively. We did not observe any association of ABI3 p.S209F with any of the other AD endophenotypes.CONCLUSION:
The results of this study highlight the importance of including biomarkers and alternative phenotypes to better understand the role of novel candidate genes with the disease.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fenótipo
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Variação Genética
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Glicoproteínas de Membrana
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Receptores Imunológicos
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Proteínas Adaptadoras de Transdução de Sinal
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Fosfolipase C gama
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Doença de Alzheimer
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Risk_factors_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
Idioma:
En
Revista:
J Alzheimers Dis
Assunto da revista:
GERIATRIA
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NEUROLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos