ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2008
Overexpression of Dyrk1A contributes to neurofibrillary degeneration in Down syndrome.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 1 of them a synthesis that pooled it.
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Who cites it
145 citing papers in PubMed, 1 synthesis or guideline pooled it, 258 citations in OpenAlex.
- Personality and risk of Alzheimer's disease: new data and meta-analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2014Pooled it
- Integrative Insights Into DYRK1A From Molecular Function to Therapeutic Advancement.Chemical biology & drug design · 2026Review
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Tau368 improves p-tau diagnostic accuracy for FTLD-tau from FTLD-TDP.Acta neuropathologica · 2026Article
- Leucettinib-21 decreases dosage effects of DYRK1A in human trisomy 21 induced pluripotent stem cell-derived neural cells.Disease models & mechanisms · 2026Article
- The CDK4/6 inhibitor abemaciclib attenuates cognitive impairment and neuroinflammation via DYRK1A in human tau transgenic mice.Molecular brain · 2026Article
- A Polypharmacology-Driven Approach to Alzheimer's Disease and Tauopathies: Rational Design, Synthesis and Characterization of Amino-Pyrazole-Based Multikinase (GSK-3β/FYN-α/DYRK1A) Inhibitors.Journal of medicinal chemistry · 2026Article
- Nitrogen-Doped Graphene Quantum Dots Conjugated to Leucettinib-21 Rescue Differentiating Zebrafish Purkinje Cells by Inhibiting Dyrk1A Kinase.ACS applied nano materials · 2026Article
- Age-related behavioral and molecular landmarks in new mouse models for studying Alzheimer's disease in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Evaluation of [Acta neuropathologica communications · 2026Article
- Measurement of Tau Protein and Aβ Amyloid Plaques in Postmortem Human Brains of Down Syndrome and Alzheimer's Disease by Using [Synapse (New York, N.Y.) · 2026Article
- Measurement of tau protein and Aβ amyloid plaques in postmortem human brains of Down syndrome and Alzheimer's disease by using [bioRxiv : the preprint server for biology · 2026Article
- Evaluation of [Research square · 2026Article
- Review
- Targeting dual specificity tyrosine-phosphorylation-regulated kinase 1A mitigates tauopathy and enhances recovery after repetitive head injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Plasma p-tau212 identifies cognitively unimpaired individuals with emerging amyloid-β pathology.Journal of neurology · 2025Article
- Cholinotrophic basal forebrain connectome dysfunction in Down syndrome with and without dementia.iScience · 2025Article
- Unlocking the Therapeutic Potential of the Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A Inhibitors in Alzheimer's Diseases.Molecular neurobiology · 2025Review
- Mitochondrial Imbalance in Down Syndrome: A Driver of Accelerated Brain Aging?Aging and disease · 2025Review
- Plasma p-tau212 as a biomarker of sporadic and Down syndrome Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
85 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
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Abstract
Adults with Down syndrome (DS) develop Alzheimer neurofibrillary degeneration in the brain, but the underlying molecular mechanism is unknown. Here, we report that the presence of an extra copy of the dual-specificity tyrosine-phosphorylated and regulated kinase 1A (Dyrk1A) gene due to trisomy 21 resulted in overexpression of Dyrk1A and elevated kinase activity in DS brain. Dyrk1A phosphorylated tau at several sites, and these sites were hyperphosphorylated in adult DS brains. Phosphorylation of tau by Dyrk1A primed its further phosphorylation by glycogen synthase kinase-3beta (GSK-3beta). Dyrk1A-induced tau phosphorylation inhibited tau's biological activity and promoted its self-aggregation. In Ts65Dn mouse brain, an extra copy of the Dyrk1A gene caused increased expression and activity of Dyrk1A and resulted in increased tau phosphorylation. These findings strongly suggest a novel mechanism by which the overexpression of Dyrk1A in DS brain causes neurofibrillary degeneration via hyperphosphorylating tau.
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