Alzheimer's disease is a neurodegenerative disease characterized by the buildup of amyloid-beta proteins in the brain, and degeneration caused by the death of neurons. This neuron death is suspected to be caused by the amyloid-B protein. People slowly lose their memory and cognitive skills. There currently is not a cure for Alzheimer's, but a few different drugs and supplements have been shown to delay or slow the onset of Alzheimer's.

The Nonsteroidal anti inflammatory drug (NSAID) Ibuprofen has shown to be therapeutic to the amyloid-B toxicity of Alzheimer's in model organisms such as mice, but it only worked as a preventative measure. Fenamate NSAIDs, such as Flufenamic acid, have been shown to be especially therapeutic in reducing the inflammation in the brain associated with Alzheimer's because in inhibits caspase-3, a major cause of apoptosis of neurons. In several studies, elevated levels of caspase-3 has been linked to an increased amount of amyloid-ß proteins in the brain.

I am testing whether the NSAIDs, Ibuprofen and Flufenamic acid, can delay the onset of the Amyloid-ß toxicity in Alzheimer's in transgenic C. elegans. I hypothesized that the NSAIDs ibuprofen and flufenamic acid would be effective in delaying Amyloid-beta induced paralysis in C. elegans (strain CL1476). To test these drugs, I am using transgenic Caenorhabditis elegans (strain CL4176). They become paralyzed as amyloid-beta builds up in their neurons, which is induced when the worms are upshifted from 16 degrees celsius to 27 degrees celsius. To compare amyloid-B toxicities in the different plates of worms, the percentage of the worms on the plates that are paralyzed after upshift are measured. In the trials, I placed the worms in conditions that emulated the solvents in my drug solutions and in the drug, all cultivated on nematode growth medium. The worms were age synchronized, and grown to the second larval stage. At the second larval stage, the worms were upshifted to 27 degrees celsius. After 18 hours of upshift, the first worms started to be paralyzed. At 18 hours and for 2 hour increments after, the percentage of the worms paralyzed on each plate was calculated up to 26 hours.

According to ANOVA, the worms treated with NSAIDs were significantly less paralyzed than all of the controls by the end, with all the controls averaging 77.,8% paralysis at 26 hours, ibuprofen at 51.3%, and flufenamic acid at 55.0%. Worms treated with ibuprofen and flufenamic acid as a preventative measure, but were shown to decrease amyloid- toxicity as the worms aged.

The NSAIDs had a positive effect on amyloid- toxicity. Unlike other studies, my data implied that NSAIDs have a greater effect when inflammation and amyloid-B toxicity is rampant, rather than preventing them. These trials suggest that amyloid-B toxicity could be triggered by inflammation, and also suggest that NSAIDs could play a role in improving Alzheimer's symptoms as the disease progresses. This experiment suggests that Alzheimer's disease could be linked to inflammation, and that NSAIDs can be used to reduce the severity of the disease.