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

Aug 13, 2008Acta neuropathologica

How High Levels of DYRK1A Protein May Link to Early Brain Cell Damage in Down Syndrome

AI simplified

Alzheimers & Treatments on OpenScience ↗PubMed ↗DOI ↗

Abstract

Higher levels of full-length DYRK1A were found in the brains of patients with Down syndrome compared to control brains.

The gene for DYRK1A is located in the Down syndrome critical region of chromosome 21.
DYRK1A is believed to play a role in abnormal brain development and neurofibrillary degeneration associated with Down syndrome.
Immunocytochemistry showed that DYRK1A accumulates in neurofibrillary tangles in both sporadic Alzheimer's disease and Down syndrome patients.
Increased levels of DYRK1A-positive neurofibrillary tangles were observed in patients with Down syndrome in a gene dosage-dependent manner.
DYRK1A is implicated in multiple forms of neurodegeneration, including granules in granulovacuolar degeneration and corpora amylacea.

AI simplified

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.

Full Text

Full text is available at the source.

View full text ↗

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

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the alzheimers & treatments brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the alzheimers & treatments brief