microRNA 155 up regulation in the CNS is strongly correlated to Down's syndrome dementia

This study examined the molecular correlates of Down's dementia. qRTPCR for chromosome 21 microRNAs was correlated with in situ hybridization, immunohistochemistry for microRNA targets, mRNAs located on chromosome 21, and neurofibrillary tangles in human and the Ts65 dn mouse Down's model....

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Bibliographic Details
Published in:Annals of diagnostic pathology 2018-06, Vol.34, p.103-109
Main Authors: Tili, Esmerina, Mezache, Louisa, Michaille, Jean-Jacques, Amann, Vicky, Williams, James, Vandiver, Paige, Quinonez, Maria, Fadda, Paolo, Mikhail, Adel, Nuovo, Gerard
Format: Article
Language:English
Subjects:
Bcl2 family
Dementia
Down's syndrome
microRNA
Tau
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Summary:This study examined the molecular correlates of Down's dementia. qRTPCR for chromosome 21 microRNAs was correlated with in situ hybridization, immunohistochemistry for microRNA targets, mRNAs located on chromosome 21, and neurofibrillary tangles in human and the Ts65 dn mouse Down's model. qRTPCR for the microRNAs on the triplicated chromosome showed miR-155 dominance in brain tissues (14.3 fold increase, human and 24.2 fold increase, mouse model) that co-expressed with hyperphosphorylated tau protein. miR-155 was not elevated in Alzheimer's disease or neonates with Downs' syndrome. Chromosome 21 genes APP/BA-42, DYRK1a and BACH1 were not correlated to pathologic changes in Down's dementia. Validated CNS targets of miR-155 that were present in controls and Alzheimer's disease but lacking in Down's dementia brains included BACH1, CoREST1, bcl6, BIM, bcl10, cyclin D, and SAPK4. It is concluded that Down's dementia strongly correlated with overexpression of chromosome 21 microRNA 155 with concomitant reduction of multiple CNS-functional targets. This study highlights the need for anatomic pathologists to determine the specific and diverse pathways cells may take to form neurofibrillary tangles in the different dementias. •The most expressed chromosome 21 miRNA in CNS of Down's dementia was -155.•The most expressed triplicated miRNA in CNS of Ts65 dn mouse model was -155.•miR-155 co expressed with neurofibrillary tangles.•Known CNS targets of miRNA-155 were down regulated in Down's dementia.•These miR-155 targets included BACH1, bcl6, blc10, CoRest1, SAPK4, BIM, and cyclin D.
ISSN:1092-9134
1532-8198
DOI:10.1016/j.anndiagpath.2018.03.006