Impact of intracellular beta-amyloid in transgenic animals and cell models

The present commentary based on cell and animal models of intracellular P-amyloid (iA beta) expression indicates that low levels of microscopically undetectable iA beta could have a physiological role in the modulation of the cyclic AMP response element (CRE)-dependent gene expression and, as a consequence, a positive influence on synaptic plasticity (the 'good'A beta?). On the other hand, high levels of iA beta resembling the pathological and microscopically visible accumulation of this amyloid peptide, akin to that observed in Down syndrome and Alzheimer's disease, disrupt CRE-regulated gene expression, therefore compromising the protein synthesis-dependent component of long-term potentiation (the 'load' A beta?). Moreover, intracellular pathology would be independent and additive to the toxic effects of the extracellular A beta burden. Copyright (c) 2008 S. Karger AG, Basel.