Inhibiting amyloid precursor protein to prevent neurodegeneration in Down syndrome and Alzheimer's disease
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Amyloid Precursor Protein (APP) is a transmembrane integral protein concentrated in neuronal synapses. APP is cleaved by proteases into multiple peptides. One of these peptides is β-amyloid. β-amyloid peptides (amino acids 1-40, and 1-42) make up the plaques that form in the brains of Alzheimer's patients. The amyloid hypothesis suggests that reducing the amount of β-amyloid would mitigate the symptoms of Alzheimer's disease. Alzheimer's disease is the fifth leading cause of death in the US, and the only one of the top ten causes of death without an effective treatment or cure. Many patients with Down syndrome also develop Alzheimer's later in life, but earlier than normal adults. Down syndrome patients have elevated APP levels since the gene for this protein is located on chromosome 21. Almost everyone with Down syndrome develops Alzheimer's due to their extra copy of of APP. Amyloid deposition associated with Alzheimer's disease is present in all Down syndrome patients older than 30. This project targets Amyloid Precursor Protein, which is implicated in the development of Alzheimer's disease and neurodegeneration in Down syndrome, byu developing an aptamer against it. Amyloid plaques and neurofibrillary tangles form in the brain of Alzheimer's patients, and the malfunction or loss of neurons causes changes in memory and brain function. Aptamers have unique advantages for medical treatment since they are highly specific, efficiently produced, can be modified for added functions, and have very low immunogenicity. This project aims to develop an aptamer against APP to help reduce the amount of plaques by reducing its functionality and preventing the creation of β-amyloid protein. By inhibiting this pathway, the formation of amyloid plaques could be reduced or perhaps even prevented. This aptamer may even help prevent the development of dementia in people with Down syndrome as they age and individuals with familial Alzheimer's disease.