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Located on chromosome 21 are the genes that encode \u03b2\u2010amyloid (A\u03b2) precursor protein (<jats:italic>APP<\/jats:italic>\u200a), a key protein involved in the pathogenesis of AD, and dual\u2010specificity tyrosine(Y)\u2010phosphorylation regulated kinase 1A (<jats:italic>DYRK1A<\/jats:italic>\u200a), a proline\u2010directed protein kinase that plays a critical role in neurodevelopment. Here, we describe a potential mechanism for the regulation of AD pathology in DS brains by DYRK1A\u2010mediated phosphorylation of APP. We show that APP is phosphorylated at Thr668 by DYRK1A <jats:italic>in vitro<\/jats:italic> and in mammalian cells. The amounts of phospho\u2010APP and A\u03b2 are increased in the brains of transgenic mice that over\u2010express the human DYRK1A protein. Furthermore, we show that the amounts of phospho\u2010APP as well as those of APP and DYRK1A are elevated in human DS brains. Taken together, these results reveal a potential regulatory link between APP and DYRK1A in DS brains, and suggest that the over\u2010expression of DYRK1A in DS may play a role in accelerating AD pathogenesis through phosphorylation of APP.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2007.05075.x","type":"journal-article","created":{"date-parts":[[2007,11,17]],"date-time":"2007-11-17T07:34:31Z","timestamp":1195284871000},"page":"1333-1344","source":"Crossref","is-referenced-by-count":215,"title":["Dual\u2010specificity tyrosine(Y)\u2010phosphorylation regulated kinase 1A\u2010mediated phosphorylation of amyloid precursor protein: evidence for a functional link between Down syndrome and Alzheimer\u2019s 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