Med, and analyzed each of the experiments. D. D. P. contributed to writing the paper. A. M. R. supplied reagents/knock-out mice and contributed to writing the paper. R. C. R. generated knock-out mice. L. D. and D. D. P. prepared the figures. L. D. prepared the tables. All authors reviewed the outcomes and authorized the final version from the manuscript.APP protects against Alzheimer’s disease and age-related cognitive decline. Nature 488, 96 9 Matsuda, S., Giliberto, L., Matsuda, Y., Davies, P., McGowan, E., Pickford, F., Ghiso, J., Frangione, B., and D’Adamio, L. (2005) The familial dementia BRI2 gene binds the Alzheimer gene amyloid- precursor protein and inhibits amyloid- production. J. Biol. Chem. 280, 289128916 Egashira, N., Iwasaki, K., Takashima, A., Watanabe, T., Kawabe, H., Matsuda, T., Mishima, K., Chidori, S., Nishimura, R., and Fujiwara, M. (2005) Altered depression-related behavior and neurochemical changes in serotonergic neurons in mutant R406W human transgenic mice. Brain Res. 1059, 72 Matsuda, S., Giliberto, L., Matsuda, Y., McGowan, E. M., and D’Adamio, L. (2008) BRI2 inhibits amyloid -peptide precursor protein processing by interfering with the docking of secretases for the substrate. J. Neurosci. 28, 8668 8676 Matsuda, S., Matsuda, Y., and D’Adamio, L. (2009) BRI3 inhibits amyloid precursor protein processing in a mechanistically distinct manner from its homologue dementia gene BRI2. J. Biol. Chem. 284, 158155825 Tanzi, R. E. (2012) The genetics of Alzheimer illness. Cold Spring Harb. Perspect. Med. two, a0066296 Vidal, R., Frangione, B., Rostagno, A., Mead, S., R z, T., Plant, G.847795-98-6 site , and Ghiso, J. (1999) A stop-codon mutation within the BRI gene associated with familial British dementia. Nature 399, 776 81 Garringer, H. J., Murrell, J., D’Adamio, L., Ghetti, B., and Vidal, R. (2010) Modeling familial British and Danish dementia. Brain Struct. Funct. 214, 23544 Vidal, R., Revesz, T., Rostagno, A., Kim, E., Holton, J. L., Bek, T., BojsenM ler, M., Braendgaard, H., Plant, G., Ghiso, J., and Frangione, B. (2000) A decamer duplication within the 3 region of your BRI gene originates an amyloid peptide that is definitely linked to dementia in a Danish kindred. Proc. Natl. Acad. Sci. U.S.A. 97, 4920 4925 De Strooper, B. (2007) Loss-of-function presenilin mutations in Alzheimer illness. talking point around the part of presenilin mutations in Alzheimer disease. EMBO Rep. 8, 14146 De Strooper, B., Vassar, R., and Golde, T. (2010) The secretases: enzymes with therapeutic prospective in Alzheimer disease. Nat. Rev. Neurol. six, 99 07 De Strooper, B., and Voet, T. (2012) Alzheimer’s illness: a protective mutation. Nature 488, 38 9 Baulac, S., LaVoie, M. J., Kimberly, W. T., Strahle, J., Wolfe, M.Price of (3,5-Difluoropyridin-2-yl)methanol S.PMID:31085260 , Selkoe, D. J., and Xia, W. (2003) Functional -secretase complex assembly in Golgi/trans-Golgi network: interactions amongst presenilin, nicastrin, Aph1, Pen-2, and -secretase substrates. Neurobiol. Dis. 14, 194 04 Borchelt, D. R., Lee, M. K., Gonzales, V., Slunt, H. H., Ratovitski, T., Jenkins, N. A., Copeland, N. G., Cost, D. L., and Sisodia, S. S. (2002) Accumulation of proteolytic fragments of mutant presenilin 1 and accelerated amyloid deposition are co-regulated in transgenic mice. Neurobiol. Aging 23, 17177 Bennett, B. D., Babu-Khan, S., Loeloff, R., Louis, J. C., Curran, E., Citron, M., and Vassar, R. (2000) Expression analysis of BACE2 in brain and peripheral tissues. J. Biol. Chem. 275, 206470651 Annaert, W., Cupers, P., Saftig, P., and De Strooper, B. (2000).
