Samuel Wadsworth

Transgenic animal models for alzheimer's disease

The neuropathology of Alzheimers disease is characterized by the deposition of abnormal protein aggregates. The main constituent of the deposition is β‐amyloid protein. A seminal role of this protein is supported by the discovery of point mutations in the gene of its precursor protein in certain forms of familial Alzheimers disease. In vitro (cultured neuronal cells), overexpression of the precursor protein or a part of the precursor leads to degeneration of neurons, suggesting neurotoxicity of its derivatives. At this tune, all of the reported transgenic mice bearing DNA construct for the precursor or a part of the precursor, however, have not developed convincing pathological changes similar to what is observed in patients with Alzheimers disease. This interesting discrepancy between in vitro and in vivo suggests suppressors in vivo which ameliorate β‐amyloid precursor protein derivative‐mediated neurotoxicity.