In vitro studies showing that DYRK1A phosphorylates tau protein suggest that this kinase is also involved in tau protein phosphorylation in the human brain and contributes to neurofibrillary degeneration, and that this contribution might be enhanced in patients with DS.
Modern research had proposed that the over expression of DYRK1A (Dual specificity tyrosine phosphorylation regulated kinase1A, a family of protein kinases, positioned within the Down's syndrome critical region (DSCR) on human chromosome 21causes phosphorylation of APP protein resulting in its cleavage to Aβ 40, 42 and tau proteins (regulated by beta and gamma secretase) which plays critical role in early onset of Alzheimer's disease (AD) detected in Down's syndrome (DS), leading to permanent functional and structural deformities which results ultimately into neuro-degeneration and neuronal death.
The different patterns of the plasma beta amyloids and tau protein may imply a different pathogenesis between DS with degeneration and AD in the general population, in spite of their common key pathological features.
Abnormally phosphorylated tau protein is the key common marker in several brain diseases such as Alzheimer's disease, Parkinson`s disease, Pick Disease, Down syndrome and frontotemporal dementia and is capable of affecting synaptic events that are critical for memory formation.
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.