This research will attempt to understand the following central cell biological questions:
- What is the sub-cellular site where Aβ is secreted?
- Can the effects of Aβ secretion on synapses be blocked by drugs?
Preliminary data show that overproduction of either axonal or dendritic Aβ reduces spine density and plasticity at dendrites close (~ 5-10 um) to the secretion sites. The effects of Aβ on spines are sensitive to blockade of nicotinic or NMDA receptors. These studies will characterize the cell biology underlying the pathogenic effects of Aβ on synapses.