The present invention describes a dissociated cell culture system
comprising cells of the hippocampus, one of the brain areas affected by
Alzheimer's Disease (AD) or amyloid beta-related diseases. This culture
system comprises hippocampal neuronal and glial cells from animal models
of AD, particularly, but not limited to, double transgenic mice
expressing both the human APP mutation (K670N:M671L) (mAPP), and the
human PS1 mutation (M146L) (mPS1), and serves as a powerful tool for the
screening and testing of compounds and substances, e.g., drugs, for their
ability to affect, treat, or prevent AD or .beta.-amyloid-related
diseases. The effects of a test substance on the cells in this culture
system can be quantitatively assessed to determine if the test substance
affects the cells biochemically and/or electrophysiologically, and/or
optically, and/or immunocytochemically. The present in vitro culture
system is advantageous for AD drug screening, because it is rapid and
efficient. By contrast, even in the fastest animal model of AD, pathology
does not start before the end of the second month. If such in vivo animal
models are used, it is necessary to wait at least the two month time
duration or longer to test for drug efficacy for AD treatment or
prevention. At the same time the present invention provides a tool for
production of amyloid-beta that can be used for electrophysiological,
behavioral, and toxicological studies.
