PT  - JOURNAL ARTICLE
AU  - Conrad C. Weihl
AU  - Ghanashyam D. Ghadge
AU  - Scott G. Kennedy
AU  - Nissim Hay
AU  - Richard J. Miller
AU  - Raymond P. Roos
TI  - Mutant Presenilin-1 Induces Apoptosis and Downregulates Akt/PKB
AID  - 10.1523/JNEUROSCI.19-13-05360.1999
DP  - 1999 Jul 01
TA  - The Journal of Neuroscience
PG  - 5360--5369
VI  - 19
IP  - 13
4099  - http://www.jneurosci.org/content/19/13/5360.short
4100  - http://www.jneurosci.org/content/19/13/5360.full
SO  - J. Neurosci.1999 Jul 01; 19
AB  - Most early onset cases of familial Alzheimer’s disease (AD) are caused by mutations in presenilin-1 (PS1) and presenilin-2 (PS2). These mutations lead to increased β-amyloid formation and may induce apoptosis in some model systems. Using primary cultured hippocampal neurons (HNs) and rat pheochromocytoma (PC12) cells transiently transfected with replication-defective recombinant adenoviral vectors expressing wild-type or mutant PS1, we demonstrate that mutant PS1s induce apoptosis, downregulate the survival factor Akt/PKB, and affect several Akt/PKB downstream targets, including glycogen synthase kinase-3β and β-catenin. Expression of a constitutively active Akt/PKB rescues HNs from mutant PS1-induced neuronal cell death, suggesting a potential therapeutic target for AD. Downregulation of Akt/PKB may be a mechanism by which mutant PS1 induces apoptosis and may play a role in the pathogenesis of familial AD.