Nucleic Acid Aptamer Selection Against Amyloid β-peptide (1-42) for the inhibition of Senile Plaques in Alzheimer’s Disease

Alyssa Koeter

Nucleic Acid Aptamer Selection Against Amyloid β-peptide (1-42) for the inhibition of Senile Plaques in Alzheimer’s Disease

Alzheimer’s is a neurodegenerative disorder that affects 5.4 million people and is the 6^thleading cause of death in the United States alone.¹ It is a form of dementia that worsens over time until a person can no longer have a conversation or respond to environmental stimuli.²
The major constituents of this disease are senile plaques and tangles that result in the death and damage of nerve cells through oxidative stress.³These plaques are present in everyone, but they are more frequent in Alzheimer’s patients.² Amyloid β-peptide makes up the majority of these plaques.³

            The specific aim of my research is to inhibit Amyloid β-peptides and therefore decrease the number of senile plaques present in Alzheimer’s patients and lessen the oxidative stress on their brains. This will be done through developing an aptamer that binds to and obstructs its production. Improper folding of the Amyloid β-peptide protein results in large insoluble masses of fragments that eventually build up into senile plaques.⁴ If there are fewer proteins, the risk of improper folding lowers and plaques are not formed. Aptamers are oligonucleic acid molecules that bind to their targets with high affinity. They are found through in-vitro selection and can be used therapeutically or diagnostically.

            The goal of my research is to find an aptamer that inhibits the reproduction of Amyloid β-Peptide and formation of senile plaques. If this is achieved, the oxidation stress on Alzheimer’s patients’ brains will be lessened and the enzyme functions of nerve cells will remain intact. As a result, most of the cells will remain alive, and the neurodegeneration will proceed at a normal aging rate rather than the accelerated one of Alzheimer’s patients.

            The target, Amyloid β-Peptide (1-42) (human), is produced by R&D Systems, and its catalog number is 1428. One hundred micrograms costs $119.00.

¹ Alzheimer's Association. 2012 “Alzheimer's disease facts and figures.” Alzheimer's and

Dementia: The Journal of the Alzheimer's Association. March 2012; 8:131–168

² Alzheimer's Association. 2012. What Is Alzheimer's? Alzheimer's and Dementia: The Journal

of the Alzheimer's Association. March 2012; 8

³ Drake, Jennifer, Christopher D. Link, and D. Allan Butterfield. "Oxidative Stress Precedes

Fibrillar Deposition of Alzheimer's Disease Amyloid β-peptide (1-42) in a Transgenic

Caenorhabditis Elegans Model." Neurobiology of Aging 24 (2003): 415-20. Elsevier, 22 Nov. 2002. Web. 3 Sept. 2012

⁴ Rahimi, Farid, and Gal Bitan. "Selection of Aptamers for Amyloid β-Protein, the Causative

Agent of Alzheimer's Disease." Journal of Visualized Experiments 39 (2010): n. pag. NCBI. PMC, 13 May 2010. Web. 4 Sept. 2012