Dual‐specificity tyrosine(Y)‐phosphorylation regulated kinase 1A‐mediated phosphorylation of amyloid precursor protein: evidence for a functional link between Down syndrome and Alzheimer’s disease

Individuals with Down Syndrome may have increased levels of phosphorylated APP and beta-amyloid in their brains.

• An extra copy of a segment of chromosome 21 in Down Syndrome is linked to early-onset Alzheimer's disease.
• DYRK1A, a protein kinase located on chromosome 21, phosphorylates the beta-amyloid precursor protein (APP) at a specific site (Thr668).
• In transgenic mice over-expressing DYRK1A, levels of phosphorylated APP and beta-amyloid are elevated.
• Human brains from individuals with Down Syndrome also show increased levels of phosphorylated APP, APP, and DYRK1A.
• These findings suggest a regulatory connection between DYRK1A and APP that could influence Alzheimer's disease progression in Down Syndrome.

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