Beta-site amyloid precursor protein cleaving enzyme 1 BACE

Willem M, Dewachter I, Smyth N, Van Dooren T, Borghgraef P, Haass C, Van Leuven F (2004) beta-site amyloid precursor protein cleaving enzyme 1 increases amyloid deposition in brain parenchyma but reduces cerebrovascular amyloid angiopathy in aging BACE x APP[V717I] double-transgenic mice. Am J Pathol 165 1621-1631. 

To elucidate potential mechanisms by which stress exacerbated Ap-induced impairment of cognitive abilities and synaptic plasticity, the levels of signaling molecules important for these processes have been evaluated. Results show that combination of chronic stress and Ap reduced the basal levels of P-CaMKII and P-CREB in area CAl of the hippocampus, more markedly than either condition alone [86, 87, 261]. Chronic nicotine treatment, on the other hand, completely prevents the effect of the combination on P-CaMKII and P-CREB levels [87, 261]. The combination of chronic stress and Ap also elevates the basal levels of calcineurin in area CAl of the hippocampus [86, 87, 260]. This elevation is also prevented by chronic nicotine treatment [87, 260]. Combination of chronic stress and Ap suppresses the expected E-LTP-induced increase in CaMKII phosphorylation and L-LTP-induced increase in CREB phosphorylation and CaMKIV protein expression in area CAl [86, 87]. These E-LTP- and L-LTP-induced expression of signaling molecules are restored by chronic nicotine treatment [87]. Furthermore, chronic stress has been shown to intensify the increase in protein levels of Ap and beta-site amyloid precursor protein [APP]-cleaving enzyme [BACE] in area CAl of Ap-treated rat. This elevation is normalized by chronic nicotine treatment [262]. Additionally, the levels of the a7, p4, and p2 subunits of nAChRs are significantly decreased in Ap rats, but these are also normalized in Ap rats chronically treated with nicotine. 

---