To determine whether apparent involvement of DYRK1A in Alzheimer's disease (AD) pathology makes it a candidate plasma biomarker for diagnosis, we developed a method to quantify plasma DYRK1A by immunoblot in transgenic mouse models having different gene dosages of Dyrk1a, and, consequently, different relative protein expression. Then, we measured plasma DYRK1A levels in 26 patients with biologically confirmed AD and 25 controls (negative amyloid imaging available on 13). DYRK1A was detected in transgenic mouse brain and plasma samples, and relative levels of DYRK1A correlated with the gene copy number. In plasma from AD patients, DYRK1A levels were significantly lower compared with controls (P<0.0001). Results were similar when we compared AD patients with the subgroup of controls confirmed by negative amyloid imaging. In a subgroup of patients with early AD (CDR=0.5), lower DYRK1A expression was confirmed. In contrast, no difference was found in levels of DYRK1B, the closest relative of DYRK1A, between AD patients and controls. Further, AD patients exhibited a positive correlation between plasma DYRK1A levels and cerebrospinal fluid tau and phosphorylated-tau proteins, but no correlation with amyloid-β42 levels and Pittsburgh compound B cortical binding. DYRK1A levels detected in lymphoblastoid cell lines from AD patients were also lower when compared with cells from age-matched controls. These findings suggest that reduced DYRK1A expression might be a novel plasma risk factor for AD.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150238 | PMC |
| http://dx.doi.org/10.1038/tp.2014.61 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Plasma p-tau212 as a biomarker of sporadic and Down Syndrome Alzheimer's disease.
medRxiv
November 2024
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
Article Synopsis
- * A new plasma test measuring p-tau212 levels shows high accuracy in detecting AD-related changes and was tested in 245 plasma and 114 cerebrospinal fluid samples using advanced technology.
- * Results indicate a strong correlation between plasma and CSF p-tau212 levels, with elevated levels in individuals with prodromal and dementia stages of DS, demonstrating high diagnostic accuracy in distinguishing between asymptomatic and symptomatic cases.
Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels.
EBioMedicine
August 2023
Faculty of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK; The London Down Syndrome Consortium (LonDownS), London, UK; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. Electronic address:
Article Synopsis
- People with Down syndrome (DS) seem to age faster than others, but scientists aren't sure why.
- A study looked at how "biological age" of people with DS compared to healthy people and found that DS individuals are, on average, around 18.4 to 19.1 years older biologically than their actual age.
- The researchers discovered that a specific gene on chromosome 21 called DYRK1A plays a big role in causing this accelerated ageing, and finding ways to reduce its effects could help people with DS.
Over-expression of Dyrk1A affects bleeding by modulating plasma fibronectin and fibrinogen level in mice.
J Cell Mol Med
August 2023
Université Paris Cité, BFA, UMR 8251, CNRS, Paris, France.
Article Synopsis
- Down syndrome is a common chromosomal disorder associated with blood issues, particularly mild to moderate thrombocytopenia (low platelet count), which doesn't typically lead to bleeding problems.
- Researchers studied the effects of Dyrk1A overexpression in mice and found it resulted in a 20% decrease in platelet count and a surprising 50% reduction in bleeding time.
- The study revealed that the changes were linked to increased levels of fibronectin and fibrinogen in the plasma and liver, suggesting Dyrk1A has a new role in promoting these proteins, which may explain the observed discrepancies in bleeding tendencies.
Increased plasma DYRK1A with aging may protect against neurodegenerative diseases.
Transl Psychiatry
April 2023
Paris Brain Institute (ICM), Centre National de la Recherche Scientifique (CNRS) UMR 7225, INSERM U1127, Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Paris, 75013, France.
Early markers are needed for more effective prevention of Alzheimer's disease. We previously showed that individuals with Alzheimer's disease have decreased plasma DYRK1A levels compared to controls. 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.
View Article and Find Full Text PDFA bivalent β-carboline derivative inhibits macropinocytosis-dependent entry of pseudorabies virus by targeting the kinase DYRK1A.
J Biol Chem
April 2023
College of Veterinary Medicine, Northwest A&F University, Xianyang, China. Electronic address:
Article Synopsis
- Pseudorabies virus (PRV) has emerged as a significant health threat since a human-strain was isolated in 2020, prompting research into effective treatments.
- A study screened 107 β-carboline derivatives, identifying 20 compounds with antiviral activity, and compound 45 demonstrated the most potent action, outperforming acyclovir.
- The mechanism of compound 45's effectiveness involves inhibiting PRV entry by targeting macropinocytosis and the kinase DYRK1A, suggesting a promising avenue for developing new anti-PRV therapies.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!