CHARACTERIZ. OF AMYLOID PRECURSOR FRAGMENTS IN PLASMA

ALZHEIMER'S DISEASE IS CURRENTLY THOUGHT TO AFFECT AS MANY AS 1 TO 3 MILLION PEOPLE IN THE UNITED STATES ALONE. IT HASRECENTLY 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 POLYPEPTIDEFRAGMENTS 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 WILLBE USED TO DEVELOP HIGHLY SENSITIVE FLUOROMETRIC IMMUNOASSAYS AGAINST VARIOUS REGIONS OF THE AMYLOID PRECURSOR. USING NUMEROUS PATIENT SAMPLES, THESE ASSAYS WILL THEN BE EVALUATED FOR THEIR DIAGNOSTIC POTENTIAL.