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Plasma DYRK1A as a novel risk factor for Alzheimer's disease.

Janel N, Sarazin M, Corlier F, Corne H, de Souza LC, Hamelin L, Aka A, Lagarde J, Blehaut H, Hindié V, Rain JC, Arbones ML, Dubois B, Potier MC, Bottlaender M, Delabar JM - Transl Psychiatry (2014)

Bottom Line: In plasma from AD patients, DYRK1A levels were significantly lower compared with controls (P<0.0001).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.

View Article: PubMed Central - PubMed

Affiliation: Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, Université Paris Diderot, EAC4413 CNRS, Paris, France.

ABSTRACT
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.

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Related in: MedlinePlus

Correlation analysis between level of CSF markers and DYRK1A level. (a) Aβ42 level and DYRK1A level; (b) tau level and DYRK1A level; (c) p-tau level and DYRK1A level. Correlation was assessed with nonparametric Spearman's rank correlation test. Graphs show regression lines with a 95% confidence interval; a.u., arbitrary unit; CSF, cerebrospinal fluid; p-tau, phosphorylated tau.
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fig4: Correlation analysis between level of CSF markers and DYRK1A level. (a) Aβ42 level and DYRK1A level; (b) tau level and DYRK1A level; (c) p-tau level and DYRK1A level. Correlation was assessed with nonparametric Spearman's rank correlation test. Graphs show regression lines with a 95% confidence interval; a.u., arbitrary unit; CSF, cerebrospinal fluid; p-tau, phosphorylated tau.

Mentions: When we analysed the correlations between plasma DYRK1A and CSF biomarkers in the AD group, we found positive correlations with both p-tau protein (P=0.02, r=0.53), and total tau (P=0.05, r=0.45), but no correlation with Aβ42 levels (P=0.06, r=0.51; Figures 4a–c). No correlation was found between PiB cortical index and DYRK1A levels.


Plasma DYRK1A as a novel risk factor for Alzheimer's disease.

Janel N, Sarazin M, Corlier F, Corne H, de Souza LC, Hamelin L, Aka A, Lagarde J, Blehaut H, Hindié V, Rain JC, Arbones ML, Dubois B, Potier MC, Bottlaender M, Delabar JM - Transl Psychiatry (2014)

Correlation analysis between level of CSF markers and DYRK1A level. (a) Aβ42 level and DYRK1A level; (b) tau level and DYRK1A level; (c) p-tau level and DYRK1A level. Correlation was assessed with nonparametric Spearman's rank correlation test. Graphs show regression lines with a 95% confidence interval; a.u., arbitrary unit; CSF, cerebrospinal fluid; p-tau, phosphorylated tau.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150238&req=5

fig4: Correlation analysis between level of CSF markers and DYRK1A level. (a) Aβ42 level and DYRK1A level; (b) tau level and DYRK1A level; (c) p-tau level and DYRK1A level. Correlation was assessed with nonparametric Spearman's rank correlation test. Graphs show regression lines with a 95% confidence interval; a.u., arbitrary unit; CSF, cerebrospinal fluid; p-tau, phosphorylated tau.
Mentions: When we analysed the correlations between plasma DYRK1A and CSF biomarkers in the AD group, we found positive correlations with both p-tau protein (P=0.02, r=0.53), and total tau (P=0.05, r=0.45), but no correlation with Aβ42 levels (P=0.06, r=0.51; Figures 4a–c). No correlation was found between PiB cortical index and DYRK1A levels.

Bottom Line: In plasma from AD patients, DYRK1A levels were significantly lower compared with controls (P<0.0001).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.

View Article: PubMed Central - PubMed

Affiliation: Unité de Biologie Fonctionnelle et Adaptative, Sorbonne Paris Cité, Université Paris Diderot, EAC4413 CNRS, Paris, France.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus