Today, more than 105 years since Alois Alzheimer identified amyloid plaques and neurofibrillary tangles, the early detection of Alzheimer’s disease is still a major challenge. There is still uncertainly about what causes Alzheimer’s disease, and according to the American Health Assistance Foundation the only way at present to definitively diagnose the disease is through a brain biopsy. This is a problem because the neurodegeneration associated with Alzheimer’s disease begins 5-10 years before symptoms warrant a diagnosis. Better and early diagnosis and pre-symptomatic treatment could therefore significantly reduce the prevalence of Alzheimer’s disease. There is no single signature characteristic that defines Alzheimer’s at early times; there is no single test.
Alzheimer’s disease develops due to a specific protein—the Alzheimer’s protein—sticking together to form protein particles. These particles then damage the normal, healthy functions of the brain. The formation of similar toxic protein particles is central to diseases such as Parkinson’s and mad cow disease. The direct imaging of protein aggregates may provide a sensitive measure of Alzheimer’s protein. However, current imaging techniques mainly targets the fibrils, formed by peptides associated with the Alzheimer’s protein, which occur late in the disease process.
In this project, the researchers aim to solve this problem by developing the reagents and sensing instrument for early detection of precursors to Alzheimer’s disease. The proposed diagnostic system will use selective binding of RNA-aptamers to target Alzheimer’s disease precursors called prefibrillar Aβ-derived oligomers. Along with discovering the RNA-aptamers that strongly and selectively bind to and distinguish Aβ1-42 oligomers, and incorporating these binders into a sensor, the research team will work with Alzheimer’s disease samples to validate the sensor.