Nucleic Acid Aptamer Selection Against S100B for the Detection and Progression of Alzheimer’s Disease

Full proposal is in Dropbox.

Final Manuscript can be found here.

Alzheimer’s, a disease in which the brain tissue slowly deteriorates, induces memory loss in millions of people worldwide. Although the cause of this fatal dementia is not yet known, S100B, a protein, could serve as a potential diagnostic or biochemical marker of brain cell damage (Raabe, 2003). S100B is expressed primarily by mature astrocytes and aid in “neurite extension, proliferation of melanoma cells, stimulation of calcium fluxes, inhibition of PKC-mediated phosphorylation, astrocytosis and axonal proliferation, and inhibition of microtubule assembly” (Raybiotech). At nanomolecular concentrations, S100B stimulates neuron growth and survival. In contrast, micromolar concentrations can lead to apoptosis, or cell death (Rothermundt, 2003). Alzheimer’s patients demonstrate an increased level of the protein in areas such as the hippocampus and temporal lobe (Eldik, 1994). Therefore, S100B levels can be used as a diagnostic marker to detect and monitor the progression of Alzheimer’s in an individual.
Figure 1) S100B protein

RNA aptamers are short strands of nucleic acids that can bind to a specific target and have the ability to accurately differentiate between related targets by a single functional group. Thus, an aptamer could bind to S100B and measure how much of the protein is contained in cerebrospinal fluid. There is growing evidence that serum levels of S100B in Alzheimer’s patients are significantly higher than those of healthy individuals (Chaves, 2010). In addition, recent studies also suggest that the level of S100B in cerebrospinal fluid can serve as a marker for brain functional condition and progression of Alzheimer’s disease (Peskind, 2001). As a result, medical examiners can utilize an aptamer to diagnose Alzheimer’s disease at an early stage, track the phases of the dementia, and possibly even improve the quality of life for these infected individuals.

The quantity of S100B found in cerebrospinal fluid can be harmless or deadly. Adequate amounts of the protein can be normal while excessive amounts lead to the on set of Alzheimer’s and eventually memory loss. An aptamer has the ability to attach precisely to the S100B protein helping doctors to monitor the protein levels and diagnose patients. The number of proteins can further tell doctors how severe the disease may be. Consequently, the selection of RNA aptamers against S100B will allow physicians to diagnose and aid their patients in ways that they have never been able to before.

Raybiotech: 100ug $149 Catalog Number: 230-000 02

Figure 2) Ample amounts of S100B can lead to the distruction of brain tissue causing memory loss and eventually Alzheimer’s. An aptamer can serve as a diagnostic marker for the diesase and even help doctors track its stages.

Chaves M., Camozzato A., Ferreira E., Piazenski I., Kochhann R., Dall’Igna O., Mazzini G., Souza D., Portela L. (2010) “Serum levels of S100B and NSE proteins in Alzheimer’s disease patients” Journal of Neuroinflammation.

Eldik L., Griffin W. (1994) “S100B expression in Alzheimer’s disease: Relation to neuropathology in brain regions” Biochimica et Biophysica Acta (BBA) – Molecular Cell Research. 1223(3): 398-403.

Peskind E., Griffin S., Akama K., Raskind M., Eldik L. (2001) “Cerebrospinal fluid S100B is elevated in the earlier stages of Alzheimer’s disease” Neurochemistry International. 39(5-6): 409-413.

Raabe, A., Kopetsh, O., Woszczyk, A., Lang, J., Gerlach, R., Zimmermann, M., Seifert, V. (2003) “Serum S-100B protein as a molecular marker in severe traumatic brain injury.” Restor Neurol Neurosci. 21(3-4): 159-169.

Rothermundt M., Peters M., Prehn JH., Arolt V. (2003) “S100B in brain damage and neurodegeneration.” Microsc Res Tech. 60(6): 614-632.



6 comments:

Gwen Stovall said...

I'm confused - I was reading your abstract, but now it's not on the site ... So - I didn't finish reading it.

There's a long quote in the first paragraph. Rewrite it in your own words & keep the citation.

Mimi Le said...

I think that you and Emma have the same project idea. I suggest you two talk to each other and to Brad to work this out.

Nia_Fernandez said...

Is there a reason this protein is prominent in the hippocampus and temporal lobe? Maybe you can give information as to what the function of those areas are.

How could the aptamers help measure the amount of protein? Is this an established method (is there background on it) or is this more of a hypothesis?

It is a very interesting project!

Brad Hall said...

Great target and you should collaborate with Emma the progress. Use different conditions (starting concentrations, buffers, etc, incubation times, etc).

Emma Weiss said...

NICE THINKING!

hahah we need to get together and talk about plans for selection...
my number is 817-287-1648

Kamaxi Patel said...

yes Emma we should!!! I'll text you soon about it all! :)