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Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology

(2013) MOLECULAR PSYCHIATRY. 18(11). p.1225-1234
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Organization
Abstract
Genome-wide association studies (GWAS) have identified a region upstream the BIN1 gene as the most important genetic susceptibility locus in Alzheimer's disease (AD) after APOE. We report that BIN1 transcript levels were increased in AD brains and identified a novel 3 bp insertion allele similar to 28 kb upstream of BIN1, which increased (i) transcriptional activity in vitro, (ii) BIN1 expression levels in human brain and (iii) AD risk in three independent case-control cohorts (Meta-analysed Odds ratio of 1.20 (1.14-1.26) (P = 3.8 x 10(-11))). Interestingly, decreased expression of the Drosophila BIN1 ortholog Amph suppressed Tau-mediated neurotoxicity in three different assays. Accordingly, Tau and BIN1 colocalized and interacted in human neuroblastoma cells and in mouse brain. Finally, the 3 bp insertion was associated with Tau but not Amyloid loads in AD brains. We propose that BIN1 mediates AD risk by modulating Tau pathology.
Keywords
Alzheimer, brain, BIN1, Drosophila, Tau, GENOME-WIDE ASSOCIATION, IDENTIFIES VARIANTS, COMMON VARIANTS, AMPHIPHYSIN-II, DISEASE, DROSOPHILA, BRAIN, PHOSPHORYLATION, ENDOCYTOSIS, MODEL

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Chicago
Chapuis, J, F Hansmannel, M Gistelinck, A Mounier, C Van Cauwenberghe, KV Kolen, F Geller, et al. 2013. “Increased Expression of BIN1 Mediates Alzheimer Genetic Risk by Modulating Tau Pathology.” Molecular Psychiatry 18 (11): 1225–1234.
APA
Chapuis, J., Hansmannel, F., Gistelinck, M., Mounier, A., Van Cauwenberghe, C., Kolen, K., Geller, F., et al. (2013). Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology. MOLECULAR PSYCHIATRY, 18(11), 1225–1234.
Vancouver
1.
Chapuis J, Hansmannel F, Gistelinck M, Mounier A, Van Cauwenberghe C, Kolen K, et al. Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology. MOLECULAR PSYCHIATRY. 2013;18(11):1225–34.
MLA
Chapuis, J, F Hansmannel, M Gistelinck, et al. “Increased Expression of BIN1 Mediates Alzheimer Genetic Risk by Modulating Tau Pathology.” MOLECULAR PSYCHIATRY 18.11 (2013): 1225–1234. Print.
@article{8547310,
  abstract     = {Genome-wide association studies (GWAS) have identified a region upstream the BIN1 gene as the most important genetic susceptibility locus in Alzheimer's disease (AD) after APOE. We report that BIN1 transcript levels were increased in AD brains and identified a novel 3 bp insertion allele similar to 28 kb upstream of BIN1, which increased (i) transcriptional activity in vitro, (ii) BIN1 expression levels in human brain and (iii) AD risk in three independent case-control cohorts (Meta-analysed Odds ratio of 1.20 (1.14-1.26) (P = 3.8 x 10(-11))). Interestingly, decreased expression of the Drosophila BIN1 ortholog Amph suppressed Tau-mediated neurotoxicity in three different assays. Accordingly, Tau and BIN1 colocalized and interacted in human neuroblastoma cells and in mouse brain. Finally, the 3 bp insertion was associated with Tau but not Amyloid loads in AD brains. We propose that BIN1 mediates AD risk by modulating Tau pathology.},
  author       = {Chapuis, J and Hansmannel, F and Gistelinck, M and Mounier, A and Van Cauwenberghe, C and Kolen, KV and Geller, F and Sottejeau, Y and Harold, D and Dourlen, P and Grenier-Boley, B and Kamatani, Y and Delepine, B and Demiautte, F and Zelenika, D and Zommer, N and Hamdane, M and Bellenguez, C and Dartigues, J-F and Hauw, J-J and Letronne, F and Ayral, A-M and Sleegers, K and Schellens, A and Broeck, LV and Engelborghs, S and De Deyn, PP and Vandenberghe, R and O'Donovan, M and Owen, M and Epelbaum, J and Mercken, M and Karran, E and Bantscheff, M and Drewes, G and Joberty, G and Campion, D and Octave, J-N and Berr, C and Lathrop, M and Callaerts, P and Mann, D and Williams, J and Bu{\'e}e, L and Dewachter, I and Van Broeckhoven, C and Amouyel, P and Moechars, D and Dermaut, Bart and Lambert, J-C},
  issn         = {1359-4184},
  journal      = {MOLECULAR PSYCHIATRY},
  language     = {eng},
  number       = {11},
  pages        = {1225--1234},
  title        = {Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology},
  url          = {http://dx.doi.org/10.1038/mp.2013.1},
  volume       = {18},
  year         = {2013},
}

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