SOLUBLE BETA-AMYLOID INDUCES ALZHEIMERS-DISEASE FEATURES IN HUMAN FIBROBLASTS AND IN NEURONAL TISSUES

It has been shown that K+ channels, Cp20 (a 20kD GTP-binding protein), and intracellular calcium release, play a key role in associative mem ory storage. These same elements have been shown to be altered in fibr oblasts from Alzheimer's Disease (AD) patients. In addition, it has be en shown that PKC, also implicated in memory storage and closely relat ed to the above mentioned components, is also altered in AD fibroblast s. Moreover, beta-amyloid was capable of inducing an AD-like phenotype for K+ channels and Cp20 in otherwise normal fibroblasts, providing a dditional evidence for the potential involvement of these components i n AD and suggesting a possible pathological consequence of soluble bet a-amyloid elevation in AD. Preliminary evidence shows that comparable changes in potassium channel function are also present in human olfact ory neuroblasts from AD patients. These results indicate that the obse rved changes not only occur in peripheral tissues such as fibroblasts, but also in neural tissue, the primary site of AD pathology.