U-p53 PEPTIDES AS MARKERS IN THE RATE OF PROGRESSION OF COGNITIVE DECLINE TO ALZHEIMER'S DISEASE

A method of classifying a subject as having a risk level selected from high risk, moderate risk, rapid progression, low risk or slow progression to Alzheimer's disease, the method comprising:

• subjecting a biological sample from said subject to immunoprecipitation using an antibody specific for U-p53 protein to provide isolated U-p53 protein;
• subjecting said isolated U-p53 protein to protease digestion to generate one or more proteolytic peptides, wherein said one or more proteolytic peptides comprises peptide P1 having SEQ ID NO:
• 1 TEEENLR;
• and
• quantifying an amount of said P1 peptide in a reaction mixture,
• wherein:
• at least 1.06 femtomoles indicates rapid progression;
• at least 0.9 femtomoles indicates high risk progression;
• at least 0.75 but less than 0.9 femtomoles indicates moderate progression or excludes high risk;
• and
• less than 0.75 femtomoles indicates low risk or slow progression,
• wherein said amount corresponds to said risk level.

A method of making a reaction mixture for classifying a subject for risk of progression to Alzheimer's disease (AD), the method comprising:

• subjecting a biological sample from said subject to immunoprecipitation using an antibody specific for p53 protein to provide isolated U-p53 protein;
• subjecting said isolated U-p53 protein to protease digestion to generate peptide P1 having SEQ ID NO:1;
• and
• forming a reaction mixture comprising said peptide P1,
• wherein said antibody comprises a heavy chain variable region comprising CDR1 (SEQ ID NO:
• 10), CDR2 (SEQ ID NO:11) and CDR3 (SEQ ID NO:12) and a light chain variable region comprising CDR1 (SEQ ID NO:13), CDR2 (SEQ ID NO:14) and CDR3 (SEQ ID NO:15),
• wherein said reaction mixture comprises an amount of said peptide P1 that:
• is at least 1.06 femtomoles, indicating rapid progression to AD;
• is at least 0.9 femtomoles, indicating high risk of progression to AD;
• is at least 0.75 femtomoles but less than 0.9 femtomoles, indicating moderate progression or exclusion of high risk;
• or
• is less than 0.75 femtomoles, indicating low risk or slow progression to AD.

A reaction mixture for assessing risk of progression to Alzheimer's disease (AD), comprising peptide P1 having SEQ ID NO:1, wherein said peptide P1 is present in an amount selected from:

• at least 1.06 femtomoles;
• at least 0.9 femtomoles;
• at least 0.75 femtomoles but less than 0.9 femtomoles;
• or
• less than 0.75 femtomoles,
• wherein said amount corresponds to rapid progression, high risk progression, moderate progression or exclusion of high risk, or low risk or slow progression to AD, respectively.