[Ionic channels and second messenger alterations in Alzheimer's disease. Relevance of studies in nonneuronal cells]

Numerous observations indicate that, while the predominant clinical expression arises from brain pathology, Alzheimer s disease (AD) has systemic expression at the cellular and molecular levels. Although these alterations seem to be inconsequential outside the central nervous system, their parallel expression in the brain could be considered a plausible pathophysiological model and explain part of the clinical manifestations; in particular those related to memory loss.

Recent research has provided experimental evidence of a direct or indirect linkage between alteration in ion channels, PKC, calcium homeostasis and amyloid processing in peripheral tissues. Some evidence also indicates similar phenomena in the brain, attesting to the relevance of the changes in non CNS cells.

Considering the difficulties of using post mortem material to study dynamic and/or early event in mostly end stage, disease ridden tissues, peripheral cells such as fibroblasts offer a model to study cellular aspects of AD pathophysiology.