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I International Symposium: Neurobiology and 
Biomarkers of Brain Aging 
microRNA in Alzheimer’s 
disease and Depression 
A...
Biomarkers 
miRNA 
Characteristics 
Advantages and 
limitations 
Major depressive 
disorder 
Alzheimer’s 
disease 
Gene th...
http://www.mdpi.com/2075-4418/3/1/84/htm
CChhaarraacctteerriissttiiccss 
• Non-coding RNA 
microRNAs mediate translational 
repression or mRNA degradation 
Post-tr...
CChhaarraacctteerriissttiiccss 
• Horizontal transfer of miRNAs by secreted 
extracellular vesicles -> intercellular commu...
CChhaarraacctteerriissttiiccss 
• A single miRNAs can target multiple mRNAs 
ARID1A 
FAM7A3 BHLHB9 
SLC10A2 
PKN2 
COPG 
h...
CChhaarraacctteerriissttiiccss 
• Multiple miRNAs can target a single mRNA 
BDNF 
hsa-miR-1 
hsa-miR-206 
hsa-miR-613 
hsa...
BBiioommaarrkkeerr 
• A biomarker is an indicator of physiological, 
biochemical, or anatomic parameter 
BBiioollooggiicca...
BBiioommaarrkkeerr 
• miRNAs can be detected in serum, plasma, 
urine, and other biological fluids 
BBooddyy fflluuiiddss ...
AAddvvaannttaaggeess 
• Horizontal transfer 
• Mature miRNAs are small 
• Stable molecules 
• Resistant to RNA degradation...
AAddvvaannttaaggeess 
• Differentiate pathological phenotypes 
• Provide global disease profiling 
• Customized treatment:...
AAddvvaannttaaggeess 
• Noninvasive biomarkers 
• Positive impact in patient comfort 
• Can lead to early diagnosis 
• Mig...
LLiimmiittaattiioonnss 
• It’s difficult to measure each miRNA contribuition to 
the disease 
• The presence of miRNAs in ...
MMeettaa--aannaallyyssiiss 
Identification 
Records identified through Web of 
Science 
Included Eligibility Screening 
Re...
AAllzzhheeiimmeerr’’ss ddiisseeaassee 
• The words used to identify the miRNAs related to 
Alzheimer’s were: Alzheimer’s d...
mmiiRRNNAAss sseeaarrcchh
NNeettwwoorrkk 
447 
genes
MMaajjoorr ddeepprreessssiivvee ddiissoorrddeerr 
• The words used to identify the miRNAs related to 
depression were: (Ma...
NNeettwwoorrkk 
210 
genes
MiRNAs common to AAllzzhheeiimmeerr’’ss ddiisseeaassee aanndd 
ddeepprreessssiioonn 
hsa-miR-26b 
hsa-miR-664 
hsa-let-7d ...
NNeettwwoorrkk
GGeennee tthheerraappyy 
• Up-regulated 
– AntagomiRs are used to decrease the levels of 
specific miRNA 
• Down-regulated...
GGeennee tthheerraappyy 
miRNAs Regulation FoldChange 
hsa-miR-766-3p Down-regulated 9,54 
hsa-miR-26b-5p Down-regulated 8...
TThhaannkk YYoouu ffoorr yyoouurr aatteennttiioonn!! 
e-mail: apmendes@ufmg.br
I International Symposium: Neurobiology and Biomarkers of Brain Aging - Micro rna in alzheimer’s disease and depression
I International Symposium: Neurobiology and Biomarkers of Brain Aging - Micro rna in alzheimer’s disease and depression
I International Symposium: Neurobiology and Biomarkers of Brain Aging - Micro rna in alzheimer’s disease and depression
I International Symposium: Neurobiology and Biomarkers of Brain Aging - Micro rna in alzheimer’s disease and depression
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I International Symposium: Neurobiology and Biomarkers of Brain Aging - Micro rna in alzheimer’s disease and depression

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I International Symposium: Neurobiology and Biomarkers of Brain Aging - Micro rna in alzheimer’s disease and depression
MicroRNAs that assist in early diagnosis of Alzheimer's and depression

Published in: Health & Medicine
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I International Symposium: Neurobiology and Biomarkers of Brain Aging - Micro rna in alzheimer’s disease and depression

  1. 1. I International Symposium: Neurobiology and Biomarkers of Brain Aging microRNA in Alzheimer’s disease and Depression Ana Paula Mendes Silva PhD Student Federal University of Minas Gerais/UFMG
  2. 2. Biomarkers miRNA Characteristics Advantages and limitations Major depressive disorder Alzheimer’s disease Gene therapy
  3. 3. http://www.mdpi.com/2075-4418/3/1/84/htm
  4. 4. CChhaarraacctteerriissttiiccss • Non-coding RNA microRNAs mediate translational repression or mRNA degradation Post-transcriptional regulators of miRNA gene expression 18 to 22-nucleotides-long http://mcb.berkeley.edu/labs/he/Research.htm
  5. 5. CChhaarraacctteerriissttiiccss • Horizontal transfer of miRNAs by secreted extracellular vesicles -> intercellular communication http://circres.ahajournals.org/content/110/3/483.abstract
  6. 6. CChhaarraacctteerriissttiiccss • A single miRNAs can target multiple mRNAs ARID1A FAM7A3 BHLHB9 SLC10A2 PKN2 COPG hsa-miR-664 ZNF423 GPHN IRF2 STRAP ARID1B CPEB4 KCMF1 KLF12 AHCTF1P MDGA2 ADCYAP1 FAM7A1 RSBN1 FRMPD4 AHCTF1 CT47A9 TTC33 SMYD1 ZMYND11 RBM26
  7. 7. CChhaarraacctteerriissttiiccss • Multiple miRNAs can target a single mRNA BDNF hsa-miR-1 hsa-miR-206 hsa-miR-613 hsa-miR-374b hsa-miR-495 hsa-miR-374a hsa-miR-10a hsa-miR-195 hsa-miR-216b hsa-miR-30a hsa-miR-122 hsa-miR-30e
  8. 8. BBiioommaarrkkeerr • A biomarker is an indicator of physiological, biochemical, or anatomic parameter BBiioollooggiiccaall PPrroocceesssseess PPaatthhoollooggiiccaall PPrroocceesssseess TThheerraappeeuuttiicc IInntteerrvveennttiioonn
  9. 9. BBiioommaarrkkeerr • miRNAs can be detected in serum, plasma, urine, and other biological fluids BBooddyy fflluuiiddss http://www.mirnabodymap.org/
  10. 10. AAddvvaannttaaggeess • Horizontal transfer • Mature miRNAs are small • Stable molecules • Resistant to RNA degradation • Highly conserved among species
  11. 11. AAddvvaannttaaggeess • Differentiate pathological phenotypes • Provide global disease profiling • Customized treatment: – Rational drug selection – Monitoring response to therapy • Alows risk stratification
  12. 12. AAddvvaannttaaggeess • Noninvasive biomarkers • Positive impact in patient comfort • Can lead to early diagnosis • Might enable patients to get on treatments earlier, preventing the devastanting effects of the disease
  13. 13. LLiimmiittaattiioonnss • It’s difficult to measure each miRNA contribuition to the disease • The presence of miRNAs in collected fluids does not directly indicate the inhibition of the translation process • Although a single miRNA can be related with multiple pathologies it does not necessarily mean that all the pathologies will develop • Cost of miRNA sequencing
  14. 14. MMeettaa--aannaallyyssiiss Identification Records identified through Web of Science Included Eligibility Screening Records identified through PubMed Records identified through SCOPUS 416 AD Records after duplicates removed 176 D Records screened Records excluded, because they are reviews, book chapters, meeting abstracts, descriptive articles and protocoll papers Full-text articles accessed for eligibility Full-text articles excluded, miRNAs specific cell, animal models and the blood of patients under the use of any medication 6 AD Studies included in the analysis 3 D http://www.prisma-statement.org/
  15. 15. AAllzzhheeiimmeerr’’ss ddiisseeaassee • The words used to identify the miRNAs related to Alzheimer’s were: Alzheimer’s disease and miRNA. • Identified 77 miRNAs differently expressed
  16. 16. mmiiRRNNAAss sseeaarrcchh
  17. 17. NNeettwwoorrkk 447 genes
  18. 18. MMaajjoorr ddeepprreessssiivvee ddiissoorrddeerr • The words used to identify the miRNAs related to depression were: (Major depressive disorder OR depressive disorder OR depression) and miRNA. • Identified 32 miRNAs differently expressed
  19. 19. NNeettwwoorrkk 210 genes
  20. 20. MiRNAs common to AAllzzhheeiimmeerr’’ss ddiisseeaassee aanndd ddeepprreessssiioonn hsa-miR-26b hsa-miR-664 hsa-let-7d hsa-let-7g 5418 115555 ggeenneess 5544 8089 hsa-miR-191 hsa-let-7f hsa-miR-30d hsa-miR-361-5p 5467 7467 6114 2015 5616
  21. 21. NNeettwwoorrkk
  22. 22. GGeennee tthheerraappyy • Up-regulated – AntagomiRs are used to decrease the levels of specific miRNA • Down-regulated – Synthetic RNAs or siRNAs are used to increase the levels
  23. 23. GGeennee tthheerraappyy miRNAs Regulation FoldChange hsa-miR-766-3p Down-regulated 9,54 hsa-miR-26b-5p Down-regulated 8,58 hsa-miR-340-5p Up-regulated 7,61 hsa-miR-6509-5p Up-regulated 7,43 cel-miR-39 Baseline (endogenous) _____________ Genome-wide sérum microRNA expression. Profiling identifies sérum biomarkers for Alzheimer’s disease. Tan, L.; Yu,J.T.; Tan, M.S.; Liu, Q.Y.; Wang, H.F.; Zhang, W.; Jiang, T. and Tan.L. Journal of Alzheimer’s disease 40 (2014) 1017-1027.
  24. 24. TThhaannkk YYoouu ffoorr yyoouurr aatteennttiioonn!! e-mail: apmendes@ufmg.br

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