SBIR-STTR Award

Alzheimer's disease is currently thought to affect as many as 1 to 3 million people in the United States alone. It has recently been found that the core A4 peptide of the senile person's plaque (one hallmark of the disease) is derived from a precursor protein 695 to 750 amino acids long. It is not known how the conversion of the precursor to the A4 protein occurs, but it is possible that specific polypeptide fragments are released into serum or cerebrospinal fluid (CSF) that could be detected by an immunoassay of appropriate specificity and sensitivity. Monoclonal antibodies will be raised to the full-length precursor molecule derived from CDNA transfected mammalian cells overexpressing the amyloid precursor. The antibodies will be characterized using an expressed precursor molecule. In addition, antisera will also be prepared from bacterially expressed fragments of the precursor molecule and corresponding synthetic peptides. These antibodies will be used to develop highly sensitive fltiorometric immunoassays against various regions of the amyloid precursor. Using numerous patient samples, these assays will then be evaluated for their diagnostic potential.

Anticipated Results:
This research aims at the development of a Alzheimer's disease diagnostic. This goal has important direct commercial applications as well as indirect therapeutic applications that might arise from understanding the changes that occur in the CSF of the Alzheimer's disease patient.National Institute on Aging

Despite recent scientific progress in Alzheimer's disease (AD) research, there currently is no accessible biochemical marker of established diagnostic value. To identify such a marker, Phase I research sought to produce monoclonal and polyclonal antibodies prepared against recombinantly expressed fragments of the B-amyloid precursor protein to attempt to identify if AD-specific fragments of the protein might exist in peripheral tissues and fluids. This has been accomplished.Phase II of this research will focus on whether the levels of the different fragments of amyloid precursor protein in blood or skin are of diagnostic utility. A recent observation has suggested that B-amyloid precursor deposits occur in the skin of AD patients. This observation will be rigorously evaluated clinically for its diagnostic potential for AD. In addition, the ability of 125I-protease nexin-II (the secreted ,B-amyloid precursor-751) to bind differentially to AD and control blood components will be assessed.Collectively, the repertoire of specific reagents that have been prepared will allow a thorough exploitation to be made of the p-amyloid precursor as a marker for a simple diagnostic testfor AD in either skin or blood.Awardee's statement of the potential commercial applications of the research:Currently in the United States alone, AD affects at least 2 to 5 million individuals with diagnosis confirmed only on autopsy. Therefore, a definitive test for AD has major commercial implications. In addition, the test has commercial and clinical value with regard to monitoring potential therapeutic treatments for this devastating disease.National Institute on Alcohol Abuse and Alcoholism (NIAAA)