The SAMP8 mouse as a model for Alzheimer disease: studies from Saint Louis University

We have studied the SAMP8 mouse over the last decade. Originally, we confirmed the memory dysfunction utilizing the aversive T-maze. We demonstrated that this was due to cholinergic, GABA, serotonergic and glutamergic function. We then showed that the SAMP8 mouse overproduced Amyloid Precursor Protein and its mRNA. Antibodies to beta-amyloid and an antisense molecule reversed the memory dysfunction seen in 12-month-old SAMP8 mice. This was in keeping with our previous finding that beta-amyloid (1-28) is amnestic in normal mice. Amyloid plaques occur in SAMP8 mice late in life (about 16 months), well after the development of memory disturbances. With microdialysis, we showed that antibodies to beta amyloid increased acetylcholine production from the hippocampus in SAMP8 mice. Male SAMP8 mice have low testosterone levels at 12 months. Testosterone replacement enhanced cognition and decreased APP. SAMP8 mice overproduce free radicals and memory is improved with alpha-lipoic acid. Finally we have shown that beta-amyloid (1 - 42) is poorly transported out of the brain of SAMP8 mice. The SAMP8 mouse is an excellent model to study memory disturbance produced by beta-amyloid production. (C) 2003 Published by Elsevier B.V.