O4-06-07

null background. We are performing A ELISAs, immunoblotting, and immunohisto-chemistry on brains from these mice and their APP transgenic controls collected at 3, 6, and 13 months of age. Results: The absence of NEP results in: a) elevations in the TBS-, NP40-, and guanidine HCl-soluble pools of brain A ; b) marked elevations in hippocampal amyloid plaque burden; and c) a dramatic increase in amyloid angiopathy. We will report further on plasma A levels, A monomer, dimer, and oligomer levels, and the possibility of a NEP gene-dose response. Conclusions: The absence of endogenous NEP in human APP transgenic mice results in elevated levels of brain A , an increased amyloid plaque burden, and the development of amyloid angiopathy.