Similar overexpression is observed in mouse models with three copies of Dyrk1a. DYRK1A transcripts from DS lymphoblastoids are overexpressed 1.4-fold compared to individuals without DS. DYRK1A is located on chromosome 21, suggesting this gene may be overexpressed in cells from individuals with Down syndrome (DS). ĭYRK1A may participate in different pathways that change over time, with an initial role during development and then other roles during adulthood and aging, and may differ across tissue types. Similarly, our results in humans also indicate an age-dependent increase of plasma DYRK1A levels, which might be protective for aging and cognitive decline. In mouse models, our work also showed increased DYRK1A levels in the brain of older wild-type mice when comparing 4-month-old with 12- and 17-month-old mice. We also recently found that plasma DYRK1A can be used to identify elderly people with subjective memory complaint who are at risk for brain amyloid β (Aβ) deposits. Our previous work showed that plasma from AD patients has significantly lower DYRK1A levels compared to controls. These processes underlie several physiological functions at different stages of life: during neurogenesis at early development, in neuronal plasticity during brain functioning, and during aging. ![]() The large number of substrates phosphorylated by DYRK1A and the wide range of interacting partners indicate that DYRK1A is capable of controlling a variety of molecular processes. DYRK1A autophosphorylates on tyrosine, serine, and threonine residues but phosphorylates its substrates only on serine and threonine residues. The gene comprises 151 kb and 15 exons (Ensemble release 90) it encodes two main protein isoforms of 763 and 754 amino acids. The kinase DYRK1A is encoded on HSA21 in 21q22.2. ![]() Therefore, there is significant interest in identifying biomarkers for individuals at increased risk of AD, who can then be targeted with preventive interventions such as risk factor reduction, behavioural modification, and pharmacologic treatment. This suggests that effective prevention will require predicting who will develop AD long before the onset of symptoms. The complex pathologic cascade that leads to Alzheimer’s disease (AD) begins decades before clinical symptoms develop. We hypothesize that lack of increase of DYRK1A at middle age (40–50 years) could be a warning before the cognitive decline, reflecting increased risk for AD. These data suggest that plasma DYRK1A levels could be used for early detection of at risk individuals of AD and for early detection of AD. Individuals with DS had higher DYRK1A levels than controls, although levels were lower in individuals with DS and with dementia. ![]() Low DYRK1A levels were also detected in patients with tauopathies. DYRK1A levels were inversely correlated with brain amyloid β burden in asymptomatic elderly individuals and AD patients. We assessed DYRK1A in the plasma of cognitively healthy elderly volunteers, individuals with either Alzheimer’s disease (AD), tauopathies or Down syndrome (DS), and in lymphoblastoids from individuals with DS. We previously showed that individuals with Alzheimer’s disease have decreased plasma DYRK1A levels compared to controls. Early markers are needed for more effective prevention of Alzheimer’s disease.
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