O1‐06‐06: Diagnosing Ad by Detecting Oligomeric Forms of Beta‐amyloid In Bodily Fluids

Alzheimer's Disease (AD), Parkinson's Diseases. Prion Diseases, Huntington's Diseases and many others are progressive neurodegenerative disorders with impairment in learning, memory, motor skills, and various cellular functions. It has been suggested that the detection of the aggregated or oligomeric forms of various biomarkers in bodily fluids would provide as robust targets for the diagnosis. In AD, the proteolytically generated amyloid beta (Aβ) peptide from the amyloid precursor protein (APP) could aggregate into insoluble fibril in senile plaques. Hence, the development of the sensitive detection methods for Aβ aggregates or oligomers in CSF or blood could be important for the therapeutic strategy and for the evaluation of the drugs, especially with upcoming releases if disease-modifying-drug candidates. Multimer Detection System (MDS) was initially developed for the detection of abnormal prion protein in blood, utilizing epitope-overlapping antibodies to create competition to discriminate oligomers from monomers. In scrapie, MDS differentiated preclinical scrapie infected sheep plasmas from normal controls. Here, MDS was used to detect spiked Aβ oligomers (SPPS) in plasma with upper nanogram/ml sensitivity. In addition, we were able to detect Aβ oligomers in bodily fluids from possible AD patients. MDS was able to differentiate Aβ oligomers from monomeric form in boldily fluids. The goal of MDS in AD is to develop promising HTS, diagnostic, prognostic assay systems for drug efficacy and therapies, and screening potential drug candidates against AD.