BrainSignsLab - Genome-wide, high-content siRNA screening identifies

Journal article

J. Chapuis, Amandine Flaig, B. Grenier‐Boley, Fanny Eysert, Virginie Pottiez, Gaspard Deloison, Alexandre Vandeputte, A. Ayral, T. Mendes, S. Desai, A. Goate, J. Kauwe, F. Leroux, Adrien Herledan, Florie Demiautte, C. Bauer, F. Checler, R. Petersen, K. Blennow, H. Zetterberg, L. Minthon, V. V. Van Deerlin, V. Lee, L. Shaw, J. Trojanowski, M. Albert, A. Moghekar, Richard O'Brien, E. Peskind, Nicolas Malmanche, G. Schellenberg, Pierre Dourlen, Ok-Ryul Song, C. Cruchaga, P. Amouyel, B. Déprez, P. Brodin, J. Lambert
Acta Neuropathologica, 2016

Semantic Scholar DOI PubMedCentral PubMed

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APA Click to copy
Chapuis, J., Flaig, A., Grenier‐Boley, B., Eysert, F., Pottiez, V., Deloison, G., … Lambert, J. (2016). Genome-wide, high-content siRNA screening identifies the Alzheimer’s genetic risk factor FERMT2 as a major modulator of APP metabolism. Acta Neuropathologica.

Chicago/Turabian Click to copy
Chapuis, J., Amandine Flaig, B. Grenier‐Boley, Fanny Eysert, Virginie Pottiez, Gaspard Deloison, Alexandre Vandeputte, et al. “Genome-Wide, High-Content SiRNA Screening Identifies the Alzheimer’s Genetic Risk Factor FERMT2 as a Major Modulator of APP Metabolism.” Acta Neuropathologica (2016).

MLA Click to copy
Chapuis, J., et al. “Genome-Wide, High-Content SiRNA Screening Identifies the Alzheimer’s Genetic Risk Factor FERMT2 as a Major Modulator of APP Metabolism.” Acta Neuropathologica, 2016.

BibTeX Click to copy

@article{j2016a,
  title = {Genome-wide, high-content siRNA screening identifies the Alzheimer’s genetic risk factor FERMT2 as a major modulator of APP metabolism},
  year = {2016},
  journal = {Acta Neuropathologica},
  author = {Chapuis, J. and Flaig, Amandine and Grenier‐Boley, B. and Eysert, Fanny and Pottiez, Virginie and Deloison, Gaspard and Vandeputte, Alexandre and Ayral, A. and Mendes, T. and Desai, S. and Goate, A. and Kauwe, J. and Leroux, F. and Herledan, Adrien and Demiautte, Florie and Bauer, C. and Checler, F. and Petersen, R. and Blennow, K. and Zetterberg, H. and Minthon, L. and Deerlin, V. V. Van and Lee, V. and Shaw, L. and Trojanowski, J. and Albert, M. and Moghekar, A. and O'Brien, Richard and Peskind, E. and Malmanche, Nicolas and Schellenberg, G. and Dourlen, Pierre and Song, Ok-Ryul and Cruchaga, C. and Amouyel, P. and Déprez, B. and Brodin, P. and Lambert, J.}
}

Abstract

Genome-wide association studies (GWASs) have identified 19 susceptibility loci for Alzheimer’s disease (AD). However, understanding how these genes are involved in the pathophysiology of AD is one of the main challenges of the “post-GWAS” era. At least 123 genes are located within the 19 susceptibility loci; hence, a conventional approach (studying the genes one by one) would not be time- and cost-effective. We therefore developed a genome-wide, high-content siRNA screening approach and used it to assess the functional impact of gene under-expression on APP metabolism. We found that 832 genes modulated APP metabolism. Eight of these genes were located within AD susceptibility loci. Only FERMT2 (a β3-integrin co-activator) was also significantly associated with a variation in cerebrospinal fluid Aβ peptide levels in 2886 AD cases. Lastly, we showed that the under-expression of FERMT2 increases Aβ peptide production by raising levels of mature APP at the cell surface and facilitating its recycling. Taken as a whole, our data suggest that FERMT2 modulates the AD risk by regulating APP metabolism and Aβ peptide production.