ALTERATION OF PROTEINS REGULATING APOPTOSIS, BCL-2, BCL-X, BAX, BAK, BAD, ICH-1 AND CPP32, IN ALZHEIMERS-DISEASE

Recently, apoptosis has been implicated in the selective neuronal loss of Alzheimer's disease (AD). Apoptosis is regulated by the B cell leu kemia-2 gene product (Bcl-2) family (Bcl-2, Bcl-x, Bax, Bak and Bad) a nd the caspase family (ICH-1 and CPP32), with apoptosis being prevente d by Bcl-2 and Bcl-x, and promoted by Bax, Bak, Bad, ICH-1 and CPP32. In the present study, we examined the levels of these proteins in the membranous and cytosolic fractions of temporal cortex in AD and contro l brain. In the membranous fraction, the levels of Bcl-2 alpha, Bcl-x( L), Bcl-x(beta), Bak and Bad were increased in AD. In the cytosolic fr actions, the level of Bcl-x(beta) was increased, while Bcl-x(L), Bax, Bak, Bad and ICH-1(L) were unchanged. CPP32 was not detected in AD or control brain. These findings demonstrate a differential involvement o f cell death-regulatory proteins in AD and suggest that Bak, Bad, Bcl- 2 and Bcl-x are upregulated in AD brains. (C) 1998 Elsevier Science B. V.