| dc.description.abstract | Alzheimer's disease is a progressive brain disorder characterized by a gradual onset of dementia. A prominent hypothesis of the cause of AD is the loss of synaptic plasticity due to amyloid-beta plaque formation in the brain. Research has shown that soluble A-beta molecules, not plaques, are responsible for disruption of synaptic function via altered processing of the amyloid precursor protein, overproduction of A-beta, suppression of postsynaptic activity through blockage of NMDA glutamate receptors, and long-term depression. Eph receptors are a family of receptor tyrosine kinases important in neurogenesis and regulation of synaptic plasticity whose levels of expression play a critical role in synaptic loss in AD. Reduction of EphB receptors results in decreased expression of NMDA receptors, increased A-beta levels, and cognitive deficit; increased EphB receptor expression has a neuroprotective effect by helping clear A-beta from the brain. This paper hypothesizes that increased levels of A-beta should be seen in hippocampal tissues of rodents lacking EphB receptors. ELISA, Western blot, and dot blots were performed to measure levels of A-beta in KO mice for EphB2 and EphB2/B3. None of the results showed the significant increase in A-beta that was hypothesized. However, it remains possible that A-beta was present in amounts too low to detect with the methods used or that Eph receptors have a cumulative effect such that knocking out more than two produces exponentially higher levels of A-beta formation. Future studies should include KO rodents for three or more Eph receptors as well as behavioral studies to assess cognitive deficit. With the number of AD cases projected to triple by 2050 and understanding of Eph receptors still largely unknown, it is important that AD research continues to be a priority in order to understand the disease and formulate treatments. | |
