Selection Against Amyloid Precursor Protein (APP), using nucleic acid aptamers, holds therapeutic and diagnostic potentials for Alzheimers Disease (AD

The full proposal has been posted on Dropbox.
Selection Against Amyloid Precursor Protein (APP), using nucleic acid aptamers, holds therapeutic and diagnostic potentials for Alzheimers Disease (AD).
AD is a neuro-degenerative disease usually affecting individuals in the latter years of life; it is also the most common form of dementia. Common symptoms include short and long term memory loss, speech impediments, and gradually loss of bodily function. Even though AD was first diagnosed over 100 years ago, there exists no definitive cure for it, and diagnostics are based on expensive and time consuming imaging technologies and neuropsychological tests [1].

Amyloid beta is a protein that is key in the progression of AD, although the specifics of the mechanism are still being researched, the hypothesis that accumulation of this peptide leads to neural degeneration is considerably valid. An effective diagnostic tool, then, would be some sort of biomarker that could target and thus detect amyloid beta. Recent studies, conducted by Rahimi and Murakami of the David Geffen School of Medicine, however, investigated the practicality of targeting beta amyloid with such aptamers, but unfortunately, did not conclude with positive results [2].

The only information gleaned from this study was the fact that aptamer’s did show some affinity towards 40 and 42 Abeta concentrations. The conclusion however was that, “aptamers for oligomeric forms of amyloidogenic proteins cannot be selected due to high, non-specific affinity of oligonucleotides for amyloid fibrils” [2].







Figure I: The Abeta formation pathway [3]

Even though Abeta binding Aptamers weren’t exactly successful, a second prevalent protein, the precursor to Abeta in fact, also has high potential for diagnostic or perhaps even therapeutic research with aptamers. As seen in Figure I above, there is a stage in the Abeta formation pathway where APP is soluble and free of amyloid fibrils. If an aptamer, with high enough affinity for APP were to be found, it could be used to signal abnormally high levels of the same, or even halt the formation of Abeta fibrils in general: essentially, either eliminating Abeta plaque formation in general, or becoming a highly effective diagnostic tool.

APP is available for order through GenScript, catalogue number RP20165, for 189.00 dollars per milligram. [4]

[1] http://en.wikipedia.org/wiki/Alzheimer's_disease#Diagnosis

[2] Rahimi, F, et al. (2010), “RNA aptamers generated against oligomeric Abeta40 recognize common amyloid aptatopes with low specificity but high sensitivity”, David Geffen School of Medicine, Department of Neurobiology, Los Angeles, California.

[3] The Trafficking and Metabolism of Amyloid Precursor Protein (APP). Digital image. Coffee Break. NCBI, 15 Sept. 1999. Web. 25 Aug. 2010. .

[4] "Beta Amyloid Peptides/ Beta Amyloid Peptide/ β Amyloid Peptide - GenScript." GenScript - Your Innovation Partner in Drug Discovery! Web. 31 Aug. 2010. .