RGD Reference Report - The role of overexpressed DYRK1A protein in the early onset of neurofibrillary degeneration in Down syndrome. - Rat Genome Database

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The role of overexpressed DYRK1A protein in the early onset of neurofibrillary degeneration in Down syndrome.

Authors: Wegiel, Jerzy  Dowjat, Karol  Kaczmarski, Wojciech  Kuchna, Izabela  Nowicki, Krzysztof  Frackowiak, Janusz  Mazur Kolecka, Bozena  Wegiel, Jarek  Silverman, Wayne P  Reisberg, Barry  Deleon, Mony  Wisniewski, Thomas  Gong, Cheng-Xin  Liu, Fei  Adayev, Tatyana  Chen-Hwang, Mo-Chou  Hwang, Yu-Wen 
Citation: Wegiel J, etal., Acta Neuropathol. 2008 Oct;116(4):391-407. doi: 10.1007/s00401-008-0419-6. Epub 2008 Aug 12.
RGD ID: 14974029
Pubmed: PMID:18696092   (View Abstract at PubMed)
PMCID: PMC2656568   (View Article at PubMed Central)
DOI: DOI:10.1007/s00401-008-0419-6   (Journal Full-text)

The gene encoding the minibrain kinase/dual-specificity tyrosine phosphorylated and regulated kinase 1A (DYRK1A) is located in the Down syndrome (DS) critical region of chromosome 21. The third copy of DYRK1A is believed to contribute to abnormal brain development in patients with DS. 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. To explore this hypothesis, the brain tissue from 57 subjects including 16 control subjects, 21 patients with DS, and 20 patients with sporadic Alzheimer's disease (AD) was examined with two antibodies to the amino-terminus of DYRK1A (7F3 and G-19), as well as two polyclonal antibodies to its carboxy-terminus (X1079 and 324446). Western blots demonstrated higher levels of full-length DYRK1A in the brains of patients with DS when compared to control brains. Immunocytochemistry revealed that DYRK1A accumulates in neurofibrillary tangles (NFTs) in subjects with sporadic AD and in subjects with DS/AD. Overexpression of DYRK1A in patients with DS was associated with an increase in DYRK1A-positive NFTs in a gene dosage-dependent manner. Results support the hypothesis that overexpressed DYRK1A contributes to neurofibrillary degeneration in DS more significantly than in subjects with two copies of the DYRK1A gene and sporadic AD. Immunoreactivity with antibodies against DYRK1A not only in NFTs but also in granules in granulovacuolar degeneration and in corpora amylacea suggests that DYRK1A is involved in all three forms of degeneration and that overexpression of this kinase may contribute to the early onset of these pathologies in DS.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Down syndrome  IEP 14974029protein:increased expression:brain:RGD 
Down syndrome  ISODYRK1A (Homo sapiens)14974029; 14974029protein:increased expression:brain:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dyrk1a  (dual specificity tyrosine phosphorylation regulated kinase 1A)

Genes (Mus musculus)
Dyrk1a  (dual-specificity tyrosine phosphorylation regulated kinase 1a)

Genes (Homo sapiens)
DYRK1A  (dual specificity tyrosine phosphorylation regulated kinase 1A)


Additional Information