Michael R. Nichols
Final Abstract for URS Program
Alzheimer's Disease (AD) is a common form of dementia that is characterized by inflammation, loss of brain mass, and loss of motor function and memory. One of the pathological hallmarks of AD is the accumulation of Amyloid-β (Aβ) in the brain as senile plaques. Aβ is formed from a large protein called Amyloid Precursor Protein (APP) when specific enzymes cut a segment of the protein into a shorter polypeptide chain, Aβ. Different aggregation species were used in this project, specifically monomers and protofibrils. Monomers are naturally occurring and nontoxic, while protofibrils are neurotoxic and neuroinflammatory. One way that Aβ can be studied is through the Indirect ELISA technique. This technique aims to determine how aggregation intermediates of Aβ interact with different antibodies. Antibodies recognize a specific sequence of the amino acid chain. Antibody (Ab) 5 and 2.1.3 were used in these experiments. Ab5 binds to the N-terminus of the polypeptide chain, while Ab2.1.3 binds to the C-terminus. The Indirect ELISA assay has aided in determining which part of the amino acid the antibody recognizes and binds to. Data obtained from Indirect ELISAs indicates that the N-terminus and C-terminus of the polypeptide is exposed on both protofibrils and monomers. However, Ab5 has a higher affinity for both protofibrils and monomers. These results give insight into the conformation of protofibrils and monomers.