(1994) found that a neuroglioma cell line expressing the Swedish FAD double mutation showed a consistent 5- to 7-fold increase in the level of the 11-kD potentially amyloidogenic C-terminal fragment. Greenberg, S. M., Shin, Y., Grabowski, T. J., Cooper, G. E., Rebeck, G. W., Iglesias, S., Chapon, F., Tournier-Lasserve, E., Baron, J.-C. Alternatively, presenilin/nicastrin-mediated gamma-secretase processing of C99 releases the amyloid-beta proteins, amyloid-beta protein 40 and amyloid-beta protein 42, major components of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59). A hybrid beta sheet, which is formed by a beta strand from APP and 2 beta strands from PS1, guides gamma-secretase to the scissile peptide bond of APP between its transmembrane and beta strand. The findings suggested that COL25A1 may play a role in the pathogenesis of Alzheimer disease. Rovelet-Lecrux, A., Hannequin, D., Raux, G., Le Meur, N., Laquerriere, A., Vital, A., Dumanchin, C., Feuillette, S., Brice, A., Vercelletto, M., Dubas, F., Frebourg, T., Campion, D. (2009) identified APP as a DR6 ligand. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer disease, Jonsson et al. Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., Beyreuther, K. Processing of APP generates a toxic amyloid β peptide that is responsible for Alzheimer's disease. Faghihi et al. The ratio of these 2 forms of beta-amyloid is important in the determination of vascular deposition as observed in CAA versus parenchymal deposition as observed in classic AD.

Tienari, P. J., Ida, N., Ikonen, E., Simons, M., Weidemann, A., Multhaup, G., Masters, C. L., Dotti, C. G., Beyreuther, K. (1991) identified it in a third Japanese family. Age-dependent beta-amyloid deposition in the APP YAC transgenic model was dramatically altered depending on the congenic strain examined. Trophic factor deprivation triggers the shedding of surface APP in a beta-secretase (BACE1; 604252)-dependent manner. (2006) proposed that A-beta-*56 impairs memory independently of plaques or neuronal loss, and may contribute to cognitive deficits associated with Alzheimer disease.

(2014) proposed that inhibitors of the interaction between beta-amyloid and fibrinogen may be useful in AD therapy. Iijima, K., Gatt, A., Iijima-Ando, K. Cisse, M., Halabisky, B., Harris, J., Devidze, N., Dubal, D. B., Sun, B., Orr, A., Lotz, G., Kim, D. H., Hamto, P., Ho, K., Yu, G.-Q., Mucke, L. Wilson, C. A., Doms, R. W., Zheng, H., Lee, V. M.-Y. PKC-delta overexpression in a mouse neuroblastoma cell line upregulated BACE1 expression and beta-amyloid protein production. (2008) showed that interaction of cyclophilin D with mitochondrial amyloid-beta protein potentiates mitochondrial, neuronal, and synaptic stress. Meyer-Luehmann, M., Spires-Jones, T. L., Prada, C., Garcia-Alloza, M., de Calignon, A., Rozkalne, A., Koenigsknecht-Talboo, J., Holtzman, D. M., Bacskai, B. J., Hyman, B. T. Cao, X., Sudhof, T. C. Wyss-Coray et al.

(2012) reported a mechanism by which pE-amyloid-beta may trigger Alzheimer disease. Ccr2 -/- mononuclear phagocytes showed normal activity and proliferation, but impaired migration in response to beta-amyloid deposition.