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DYRK1A and Activity-Dependent Neuroprotective Protein Comparative Diagnosis Interest in Cerebrospinal Fluid and Plasma in the Context of Alzheimer-Related Cognitive Impairment in Down Syndrome Patients
Moreau M, Carmona-Iragui M, Altuna M, Dalzon L, Barroeta I, Vilaire M, Durand S, Fortea J et al.. Biomedicines, 2022-06-10
Topic: Brain proteins, microglia and lab models
Down syndrome (DS) is a complex genetic condition due to an additional copy of human chromosome 21, which results in the deregulation of many genes. In addition to the intellectual disability associated with DS, adults with DS also have an ultrahigh risk of developing early onset Alzheimer's disease dementia. DYRK1A, a proline-directed serine/threonine kinase, whose gene is located on chromosome 21, has recently emerged as a promising plasma biomarker in patients with sporadic Alzheimer's disease (AD). The protein DYRK1A is truncated in symptomatic AD, the increased truncated form being associated with a decrease in the level of full-length form. Activity-dependent neuroprotective protein (ADNP), a key protein for the brain development, has been demonstrated to be a useful marker for symptomatic AD and disease progression. In this study, we evaluated DYRK1A and ADNP in CSF and plasma of adults with DS and explored the relationship between these proteins. We used mice models to evaluate the effect of DYRK1A overexpression on ADNP levels and then performed a dual-center cross-sectional human study in adults with DS in Barcelona (Spain) and Paris (France). Both cohorts included adults with DS at different stages of the continuum of AD: asymptomatic AD (aDS), prodromal AD (pDS), and AD dementia (dDS). Non-trisomic controls and patients with sporadic AD dementia were included for comparison. Full-form levels of DYRK1A were decreased in plasma and CSF in adults with DS and symptomatic AD (pDS and dDS) compared to aDS, and in patients with sporadic AD compared to controls. On the contrary, the truncated form of DYRK1A was found to increase both in CSF and plasma in adults with DS and symptomatic AD and in patients with sporadic AD with respect to aDS and controls. ADNP levels showed a more complex structure. ADNP levels increased in aDS groups vs. controls, in agreement with the increase in levels found in the brains of mice overexpressing DYRK1A. However, symptomatic individuals had lower levels than aDS individuals. Our results show that the comparison between full-length and truncated-form levels of DYRK1A coupled with ADNP levels could be used in trials targeting pathophysiological mechanisms of dementia in individuals with DS.
Key findings
- Down syndrome (DS) is a complex genetic condition due to an additional copy of human chromosome 21, which results in the deregulation of many genes.
- In addition to the intellectual disability associated with DS, adults with DS also have an ultrahigh risk of developing early onset Alzheimer's disease dementia.
- The protein DYRK1A is truncated in symptomatic AD, the increased truncated form being associated with a decrease in the level of full-length form.
- Activity-dependent neuroprotective protein (ADNP), a key protein for the brain development, has been demonstrated to be a useful marker for symptomatic AD and disease progression.
- Full-form levels of DYRK1A were decreased in plasma and CSF in adults with DS and symptomatic AD (pDS and dDS) compared to aDS, and in patients with sporadic AD compared to controls.
Why it matters
This cross-sectional study in adults with Down syndrome examined DYRK1A and ADNP in CSF and plasma across stages of Alzheimer-related cognitive impairment, with supporting mouse work. It is about biomarker evaluation and does not test any treatment, cure or prevention.
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Study details
- Study designcross-sectional
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biomedicines) |
| Journal's citation record | 1 / 4 | Biomedicines: journal h-index 133 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 10 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.7 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 2 / 6 | Cited 1.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Nathalie Janel: h-index 33 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Centre National de la Recherche Scientifique: institution h-index 2,511 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35740400) |
| Free to read | 2 / 2 | Free to read |
| Total | 43 / 100 | — |
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Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Moreau, M., Carmona-Iragui, M., Altuna, M., Dalzon, L., Barroeta, I., Vilaire, M., et al. (2022). DYRK1A and Activity-Dependent Neuroprotective Protein Comparative Diagnosis Interest in Cerebrospinal Fluid and Plasma in the Context of Alzheimer-Related Cognitive Impairment in Down Syndrome Patients. Biomedicines. https://doi.org/10.3390/biomedicines10061380
Vancouver
Moreau M, Carmona-Iragui M, Altuna M, Dalzon L, Barroeta I, Vilaire M, et al. DYRK1A and Activity-Dependent Neuroprotective Protein Comparative Diagnosis Interest in Cerebrospinal Fluid and Plasma in the Context of Alzheimer-Related Cognitive Impairment in Down Syndrome Patients. Biomedicines. 2022. doi:10.3390/biomedicines10061380. PMID: 35740400.
BibTeX
@article{moreau2022-35740400,
author = {Moreau, M. and Carmona-Iragui, M. and Altuna, M. and Dalzon, L. and Barroeta, I. and Vilaire, M. and Durand, S. and Fortea, J. and others},
title = {{DYRK1A and Activity-Dependent Neuroprotective Protein Comparative Diagnosis Interest in Cerebrospinal Fluid and Plasma in the Context of Alzheimer-Related Cognitive Impairment in Down Syndrome Patients}},
journal = {Biomedicines},
year = {2022},
doi = {10.3390/biomedicines10061380},
pmid = {35740400},
url = {https://doi.org/10.3390/biomedicines10061380}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.