Bridging Integrator 1 (BIN1) Genotypes Mediate Alzheimer's Disease Risk by Altering Neuronal Degeneration.
J Alzheimers Dis
; 52(1): 179-90, 2016 03 15.
Article
en En
| MEDLINE
| ID: mdl-27003210
ABSTRACT
BACKGROUND:
Bridging integrator 1 (BIN1) has been identified as one of the most associated loci for Alzheimer's disease (AD), and recently was reported to modulate tau pathology to mediate AD in vitro. However, the effects of BIN1 on the AD related biomarkers in AD continuum were not specifically assessed.OBJECTIVE:
We explored the effects of BIN1 loci on AD specific biomarkers (CSF proteins, brain structures, glucose and amyloid-ß (Aß) metabolisms) to investigate the role BIN1 in AD pathogenesis.METHODS:
We calculated the associations of BIN1 loci with these markers at baseline and follow-up in multiple linear models in 812 ADNI subjects.RESULTS:
BIN1 loci were significantly associated with the levels of T-tau (rs744373 pcâ=â0.047, rs13031703 pcâ=â0.042) and P-tau (rs744373 pcâ=â0.044, rs13031703 pcâ=â0.019), but not with Aß in CSF test. BIN1 genotypes were strongly related to atrophy of hippocampus (rs7561528 pcâ=â0.011), CA1 (rs1469980 pcâ=â0.029) and parahippocampus (rs72838284, pcâ=â0.017) on MRI, and to glucose metabolism on FDG-PET, but not to Aß deposition on AV45-PET imaging. Furthermore, haplotype and subgroup analysis confirmed these significant findings. In addition, the loci associated with these markers were also identified to influence the risk for AD in the meta-analysis of 74 046 European individuals.CONCLUSION:
This study supported that BIN1 contributes to the risk of AD by altering neural degeneration (abnormal tau, brain atrophy and glucose metabolism) but not Aß pathology.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
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Proteínas Nucleares
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Predisposición Genética a la Enfermedad
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Proteínas Supresoras de Tumor
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Proteínas Adaptadoras Transductoras de Señales
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Enfermedad de Alzheimer
Tipo de estudio:
Clinical_trials
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Límite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Alzheimers Dis
Asunto de la revista:
GERIATRIA
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NEUROLOGIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
China