Tthe proposal must include a brief introduction to the research topic , summarizing what is known and what remains elusive in the field. Then state the problem/question you will address, give your hypothesis based on current knowledge, explain its rationale, and propose three different biochemical approaches that you are going to use to solve the puzzle. This proposal should present substantial information from at least five recent research papers and one review paper from leading refereed biochemical journals. None of these papers should be more than four years old. Background would need to focus on the synapses and why they are important. A hypothesis needs to focus on a single aspect of research: in my case, it focus on the loss of proper synapsis. in the approach section: 1) A better first experiment would be using proteomics/mass spec to identify protein expression differences between normal brain cells and AD-affected cells and specifically looking for differences in synapse-related proteins. 2). If there are already synaptic proteins implicated in AD, these would be appropriate to probe for. You could also use the results of the mass spec to narrow down which proteins you will probe for. 3) You need to use AD cells, or tissue derived from AD patients, This would also be more suited to proteomics: knock down certain synapse proteins in healthy cells and quantify the levels of Tau protein compared to “normal” AD cells. When you get to experimental design, remember that you first have to identify differences between normal and AD cells before moving forward. Western blots are better suited for comparing a few specific proteins rather than searching through the entire proteome for any differences. One thing that may help is looking into more detail of which synaptic proteins are known to be affected in AD and other similar diseases – then you can compare those levels to healthy cells.