Cargando…

The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory

The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer’s disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is medi...

Descripción completa

Detalles Bibliográficos
Autores principales: Franzmeier, Nicolai, Rubinski, Anna, Neitzel, Julia, Ewers, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467911/
https://www.ncbi.nlm.nih.gov/pubmed/30992433
http://dx.doi.org/10.1038/s41467-019-09564-5
_version_ 1783411324454174720
author Franzmeier, Nicolai
Rubinski, Anna
Neitzel, Julia
Ewers, Michael
author_facet Franzmeier, Nicolai
Rubinski, Anna
Neitzel, Julia
Ewers, Michael
author_sort Franzmeier, Nicolai
collection PubMed
description The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer’s disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Here we find in 89 older individuals without dementia, that BIN1 rs744373 risk-allele carriers show higher AV1451 tau-PET across brain regions corresponding to Braak stages II–VI. In contrast, the BIN1 rs744373 SNP was not associated with AV45 amyloid-PET uptake. Furthermore, the rs744373 risk-allele was associated with worse memory performance, mediated by increased global tau levels. Together, our findings suggest that the BIN1 rs744373 SNP is associated with increased tau but not beta-amyloid pathology, suggesting that alterations in BIN1 may contribute to memory deficits via increased tau pathology.
format Online
Article
Text
id pubmed-6467911
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-64679112019-04-18 The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory Franzmeier, Nicolai Rubinski, Anna Neitzel, Julia Ewers, Michael Nat Commun Article The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer’s disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Here we find in 89 older individuals without dementia, that BIN1 rs744373 risk-allele carriers show higher AV1451 tau-PET across brain regions corresponding to Braak stages II–VI. In contrast, the BIN1 rs744373 SNP was not associated with AV45 amyloid-PET uptake. Furthermore, the rs744373 risk-allele was associated with worse memory performance, mediated by increased global tau levels. Together, our findings suggest that the BIN1 rs744373 SNP is associated with increased tau but not beta-amyloid pathology, suggesting that alterations in BIN1 may contribute to memory deficits via increased tau pathology. Nature Publishing Group UK 2019-04-16 /pmc/articles/PMC6467911/ /pubmed/30992433 http://dx.doi.org/10.1038/s41467-019-09564-5 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Franzmeier, Nicolai
Rubinski, Anna
Neitzel, Julia
Ewers, Michael
The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory
title The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory
title_full The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory
title_fullStr The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory
title_full_unstemmed The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory
title_short The BIN1 rs744373 SNP is associated with increased tau-PET levels and impaired memory
title_sort bin1 rs744373 snp is associated with increased tau-pet levels and impaired memory
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467911/
https://www.ncbi.nlm.nih.gov/pubmed/30992433
http://dx.doi.org/10.1038/s41467-019-09564-5
work_keys_str_mv AT franzmeiernicolai thebin1rs744373snpisassociatedwithincreasedtaupetlevelsandimpairedmemory
AT rubinskianna thebin1rs744373snpisassociatedwithincreasedtaupetlevelsandimpairedmemory
AT neitzeljulia thebin1rs744373snpisassociatedwithincreasedtaupetlevelsandimpairedmemory
AT ewersmichael thebin1rs744373snpisassociatedwithincreasedtaupetlevelsandimpairedmemory
AT thebin1rs744373snpisassociatedwithincreasedtaupetlevelsandimpairedmemory
AT franzmeiernicolai bin1rs744373snpisassociatedwithincreasedtaupetlevelsandimpairedmemory
AT rubinskianna bin1rs744373snpisassociatedwithincreasedtaupetlevelsandimpairedmemory
AT neitzeljulia bin1rs744373snpisassociatedwithincreasedtaupetlevelsandimpairedmemory
AT ewersmichael bin1rs744373snpisassociatedwithincreasedtaupetlevelsandimpairedmemory
AT bin1rs744373snpisassociatedwithincreasedtaupetlevelsandimpairedmemory