Methods of using miRNA from bodily fluids for early detection and monitoring of mild cognitive impairment (MCI) and Alzheimer's disease (AD)

A method for identifying a compound useful for slowing down the progression of or treating pre-MCI or MCI, which method comprises:

• a. measuring the level of at least one synapse or neurite miRNA in one or more bodily fluid samples collected from a subject having pre-MCI or MCI, wherein the synapse or neurite miRNA is selected from the group consisting of miR-7, miR-125b, miR-128, miR-132, miR-874, miR-134, miR-323-3p, and miR-382, wherein said bodily fluid sample(s) is collected prior to test compound administration and wherein the bodily fluid is selected from the group consisting of blood plasma, serum, urine, and saliva;
• b. measuring the level of a normalizer miRNA in the same bodily fluid sample(s) as in step (a), wherein the normalizer miRNA is selected from the group consisting of miR-9, miR-181a, miR-127-3p, miR-370, miR-141, and miR-491-5p;
• c. calculating the ratio of the level of the synapse or neurite miRNA measured in step (a) to the level of the normalizer miRNA measured in step (b) for each of the bodily fluid samples collected from the subject prior to a test compound administration;
• d. measuring the level of the same synapse or neurite miRNA(s) as in step (a) in one or more bodily fluid samples collected from the subject following administration of the test compound, wherein the bodily fluid is selected from the group consisting of blood plasma, serum, urine, and saliva;
• e. measuring the level of the same normalizer miRNA as in step (b) in the same bodily fluid sample(s) as in step (d);
• f. calculating the ratio of the level of the synapse or neurite miRNA measured in step (d) to the level of the normalizer miRNA measured in step (e) for each of the bodily fluid samples collected from the subject following administration of the test compound;
• g. comparing the ratios of the levels of the miRNAs calculated in steps (c) and (f), and
• h. (i) identifying the test compound as a candidate compound for slowing down the progression of or treating pre-MCI or MCI if the ratio of the levels of the miRNAs calculated in step (f) is lower than the ratio of the levels of the miRNAs calculated in step (c);
• (ii) identifying the test compound as not a candidate compound for slowing down the progression of or treating pre-MCI or MCI if the ratio of the levels of the miRNAs calculated in step (f) is not lower than the ratio of the levels of the miRNAs calculated in step (c).