We have validated a set of three plasma microRNAs statistically associated Parkinsons disease in both female and male patients.

Name    Fold change    Pvall

miR-A       1.26          0.015

miR-B      1.23          0.028

   miR-C      1.47          0.005  

Our analysis of age and gender specific epression of these three microRNAs in WT mice reveals organ, gender and age specific expression patterns, which partially correlates with the age and gender analysis performed in humans. A second (ongoing) analysis of the corresponding pri-miR expression will provide info upon the transcriptional aspects of microRNA regulation in these organs.

Here is the final analysis (91 participants) of the entire set of 15 microRNAs

Name          Fold change        Pvall

miR-A               1.27               0.011

miR-B               1.24                0.022

miR-C               1.47               0.005

miR-16                1.1               0.197

miR-92a               1.26              0.071

miR-576-5p      1.33              0.134

miR-16-2*           0.96              0.854

miR-941            1.12              0.702

miR-363             1.16              0.517

miR-454            0.95              0.836

let-7e               0.93               0.770

let-7c               0.96               0.882

let-7b               1.09               0.694

miR-93*            0.88             0.5454

miR-1976               0.67             0.170

Characterization of diagnostic tests for the 3 plasma microRNAs associated to Parkinson's disease

miR-A   

Sensitivity (CI 95%) 91.04 (81.5-96.6)

Specificity (CI 95%) 32.35 (17.4-50.5)

Accuracy (CI 95%) 71.29 (61.4-79.9)

miR-B

Sensitivity (CI 95%) 89.39 (79.4-95.6)

Specificity (CI 95%) 31.43 (16.9-49.3)

Accuracy (CI 95%) 69.31 (59.3-78.1)

miR-C

Sensitivity (CI 95%) 74.24 (62.0-84.0)

Specificity (CI 95%) 57.14 (39.4-73.7)

Accuracy (CI 95%) 68.32 (58.3-77.2)

Age specific variations of mature miR-B and miR-C in the brain of WT mice

miR-C (ratios to neonatal value)

Age             Fold change          Pvalue

3m                   2.53                     0.002

6m                    8.88                    0.002

9m                    2.59                   0.012

21m                   9.58                   0.017 

miR-B (ratios to neonatal value)

Age                Fold change           Pvalue

3m                        0.04                 0.002

6m                       0.01             0.00005

9m                        0.005                   0.03

21m                      0.06                  0.001

Bioinformatics analysis (miRWalk3.0/David) of  miR-A, miR-B and miR-C targets

KEGG path     Pval     Enrichment   Benjamini

hsa04022     5.9E-05          1.5            0.017

hsa04015      1.09E-04       1.44           0.016