Diagnosing mild cognitive impairment (MCI), predicting alzheimer's disease (AD) dementia onset, and screening and monitoring agents for treating mci or preventing dementia onset

A method for predicting the time to clinical onset of Alzheimer's disease (AD) dementia in a test subject having Mild Cognitive Impairment (MCI) comprising

• (a) obtaining cells from the test subject;
• (b) contacting a first portion of the cells with a Protein Kinase C (PKC) activator while leaving a second portion of the cells uncontacted with the PKC activator,
• wherein the PKC activator is selected from the group consisting of bradykinin, a bryostatin, a bryolog, neristatin, 8-[2-(2-pentyl-cyclopropylmethyl)cyclopropyl]-octanoic acid (DCPLA), and esters of DCPLA;
• (c) determining an output signal of AD Index Biomarker using the cells from the test subject by using levels of phosphorylated extracellular signal-regulated kinase 1 (pERK1) and phosphorylated extracellular signal-regulated kinase 2 (pERK2), wherein the output signal is determined by
• calculating a first ratio of pERK1 to pERK2 in the first portion of the cells,
• calculating a second ratio of pERK1 to pERK2 in the second portion of the cells, and
• subtracting the second ratio from the first ratio to obtain the output signal of AD Index Biomarker;
• (d) obtaining a graph of AD Index Biomarker values, the graph having plotted thereon:
• first AD Index Biomarker values for cells obtained from AD-afflicted subjects and
• second AD Index Biomarker values for cells obtained from age-matched control subjects,
• wherein
• the graph has as its x-axis age difference in years and has as its y-axis AD Index values from 0-100,
• the graph includes an inflection point between the first AD Index Biomarker values and the second AD Index Biomarker values;
• and
• the first AD Index Biomarker values and the second AD Index Biomarker values are obtained using levels of pERK1 and pERK2 in the cells obtained from AD-afflicted subjects and in the cells obtained from the age-matched control subjects, respectively;
• and
• (e) plotting the output signal determined in step (c) on the graph obtained in step (d), and predicting the time to clinical onset of AD dementia in the test subject based on the position of the output signal determined in step (c) on the graph relative to the inflection point,
• wherein
• the age difference for each AD-afflicted subject is the difference in age between the time of clinical onset of AD and the age at the time of collecting cells, and
• the age difference for each age-matched control subject is the difference in age between the age at the time of collecting cells from the age-matched control subject and the age of the oldest age-matched control subject at the time of collecting cells from that subject.