Beta-site APP cleaving enzyme 1 (BACE1) is increased in remaining neurons in Alzheimer's disease brains

Alzheimer's disease (AD) is characterized by the extensive deposition of amyloid beta protein (A beta) in the brain cortex. A beta is produced from beta-amyloid precursor protein (APP) by beta-secretase and gamma-secretase. beta-Secretase has been identified as beta-site APP cleaving enzyme I (BACE I), We produced rabbit polyclonal antibodies against the amino and the carboxyl terminals of BACE1. Using these anti bodies, BACE1 was characterized in temporal lobe cortices by Western blotting and immunohistochemistry. Immumohistochemical studies employing anti-GFAP and anti-MAP2 antibodies as well its anti-BACE1 antibodies showed that BACE1 was expressed exclusively in neurons but not in glial cells. Brain samples were directly extracted by 0.5% SDS and analyzed by Western blotting and densitometer. Although the mean level of BACE 1/mg protein in AD brains was not increased, the ratio of BACE1 to MAP2 or to NSE was significantly increased compared with that in control brains. Taken together, these findings suggest that those neurons that survive in AD brains might generate more BACE I than normal neurons in control brains, indicating that increased BACE1 activity could be one of the causes of AD. This could justify the development of anti-BACE1 drugs for AD treatment. (c) 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.