Nucleic Acid Aptamer
Selection Against Amyloid Precursor Protein to Prevent Neurodegeneration in
Down’s Syndrome and Alzheimer’s Disease
Charisma DeSai - Fall 2013
Charisma DeSai - Fall 2013
In the United States, approximately 5.2 million people have
Alzheimer’s Disease and more than 400,000 individuals have Down’s Syndrome (Texas
Department of State Health Services) (National Down Syndrome Society). These
conditions are well-known, but as of yet, no definitive
cause or cure has been found for either. Alzheimer’s disease is the most common
form of dementia in the human population. Amyloid plaques and neurofibrillary
tangles form in the brain, and the malfunction or loss of neurons causes
changes in memory and brain function. Many patients with Down’s syndrome also
develop Alzheimer’s later in life, but earlier than normal adults. Amyloid
deposition associated with Alzheimer’s disease is present in all Down’s
syndrome patients older than 30 (Egensperger 113).
Amyloid
precursor protein (APP) is a transmembrane glycoprotein that is spliced into
multiple peptides. Evidence suggests that APP and its derivative, beta amyloid,
may contribute to Alzheimer’s disease. The beta amyloid protein makes up the
plaques that form in the brains of Alzheimer’s patients. The amyloid hypothesis
states that accumulation of beta-amyloid in the brain is the primary cause of
Alzheimer’s disease pathogenesis (Hermey 8). Down’s syndrome patients have
elevated APP levels since the gene for this protein is located on chromosome 21
(Arai 290). A small minority of Alzheimer’s disease patients (approximately
five percent) have an inherited form of the disease associated with an
autosomal dominant disorder that is linked to mutations in the genes APP (Van
Dijk 712).
The amyloid hypothesis suggests that reducing the amount of
beta-amyloid would mitigate the symptoms of Alzheimer’s disease (Hermey 8). 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. An aptamer against APP would help reduce the amount of
plaques by reducing its functionality and preventing the creation of beta amyloid
protein. By inhibiting this pathway, the
formation of plaques from the beta amyloid protein could be reduced or perhaps
even prevented. This aptamer may even help prevent the development of dementia
in people with Down’s syndrome as they age or individuals with familial
Alzheimer’s disease.
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Figure 1. The role of Amyloid
Precursor Protein, which is cleaved into beta amyloid protein. By inhibiting
APP, formation of amyloid plaques in the brain and neuronal death could be
prevented.
Specific Aim
1: Selection
of RNA aptamers against Amyloid Precursor Protein
The Amyloid
Precursor Protein (APP) differentiates into multiple proteins. One of these is
beta amyloid, which leads to the formation of plaques in the brain and
consecutive nerve cell death. Thus, the selection of RNA aptamers against APP
will inhibit the role of beta amyloid in neuronal death.
Ordering information:
Vendor: My Bio Source
Product Catalog
number: MBS204227
Vendor Website:
http://www.mybiosource.com/datasheet.php?products_id=204227
Vendor
Telephone: 1-858-633-0165
Cost per Unit:
100 µg for $335
Cost per round:
$23.26
Sources:
"Alzheimer's Disease - Questions and Answers." Alzheimer'
S Disease Questions and Answers. Texas Department of State Health Services,
14 May 2013. Web. 20 Aug. 2013.
Arai, Y., Suzuki, A., Masashi, M., and Takashima, S. "Developmental and aging changes
in the expression of amyloid precursor protein in Down syndrome brains." Brain
and Development 19.4 (1997): 290-294.
"Down Syndrome Facts." NDSS.org. National
Down Syndrome Society, 2012. Web. 01 Sept. 2013.
Egensperger, R., Weggen, S. Multhaup, N., Schnabel, F., Beyreuther, K., and Bayer, T. "Reverse relationship
between β-amyloid precursor protein and β-amyloid peptide plaques in Down’s
syndrome versus sporadic/familial Alzheimer’s disease." Acta
neuropathologica 97.2 (1999): 113-118.
Hermey, Guido. "Targeting amyloid precursor
protein." Annals of neurology 69.1 (2011): 8-10.
Roizen, N. J., and Patterson, D. "Down's
syndrome." The Lancet 361.9365 (2003): 1281-1289.
Van Dijk, R., Fischer, D., Sluijs, J., Sonnemans, M., Hobo, B., Mercken, L., Mann, D., Hol, E., and van Leeuwen, F. "Frame shifted amyloid precursor
protein found in Alzheimer's disease and Down's syndrome increases levels of
secreted amyloid β40." Journal of neurochemistry 90.3 (2004):
712-723.
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