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Increased MAP kinase activity in Alzheimer's and Down syndrome but not in schizophrenia human brain
Swatton JE, Sellers LA, Faull RL, Holland A, Iritani S, Bahn S.. The European journal of neuroscience, 2004-05-01
Topic: Disease mechanisms in lab and animal studies
Abnormal phosphorylation of tau is a feature of Alzheimer's disease (AD), which develops prematurely in Down syndrome (DS) patients. Cognitive impairment is also recognized as a clinical characteristic of schizophrenia, which does not appear to be associated with tau-aggregate formation. Several kinases can phosphorylate tau in cell-free assays. Here we show increased activity of mitogen-activated protein kinases (MAPKs) (including ERK1/2, SAPKs and p38) in post mortem AD and DS brains, which could not be accounted for by expression changes. In contrast, glycogen synthase kinase-3 activity (GSK-3 alpha beta) was reduced significantly. Examination of tau in AD and DS using antibodies selective for MAPK phosphorylation sites showed increased immunoreactivity. In addition, phosphorylation of S(199), reportedly a selective substrate for cyclin-dependent kinase-5 (cdk5) or GSK-3 alpha beta was only observed in AD samples, which showed a concomitant increase in the expression of p25, the enhancing cofactor for cdk5 activity. However, in schizophrenia brain, MAPK-phosphorylated tau was unchanged compared to matched controls, despite similar expression levels to those in AD. The activities of the MAPKs and GSK-3 alpha beta were also unchanged. These data demonstrate that in AD and DS, enhanced MAPK activity, which has an established role in regulating neuronal plasticity and survival, can account for irregular tau phosphorylation, and that the molecular processes involved in these neurodegenerative disorders are distinct from those in schizophrenia. These data also question the significance of GSK-3 alpha beta, as much previous work carried out in vitro has placed this kinase as a favoured candidate for involvement in the pathological phosphorylation of tau.
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APA 7th
Swatton, J. E., Sellers, L. A., Faull, R. L., Holland, A., Iritani, S., & Bahn, S. (2004). Increased MAP kinase activity in Alzheimer's and Down syndrome but not in schizophrenia human brain. The European journal of neuroscience. https://doi.org/10.1111/j.0953-816x.2004.03365.x
Vancouver
Swatton JE, Sellers LA, Faull RL, Holland A, Iritani S, Bahn S. Increased MAP kinase activity in Alzheimer's and Down syndrome but not in schizophrenia human brain. The European journal of neuroscience. 2004. doi:10.1111/j.0953-816x.2004.03365.x. PMID: 15147305.
BibTeX
@article{swatton2004-15147305,
author = {Swatton, J. E. and Sellers, L. A. and Faull, R. L. and Holland, A. and Iritani, S. and Bahn, S.},
title = {{Increased MAP kinase activity in Alzheimer's and Down syndrome but not in schizophrenia human brain}},
journal = {The European journal of neuroscience},
year = {2004},
doi = {10.1111/j.0953-816x.2004.03365.x},
pmid = {15147305},
url = {https://doi.org/10.1111/j.0953-816x.2004.03365.x}
}
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Key findings
- Cognitive impairment is also recognized as a clinical characteristic of schizophrenia, which does not appear to be associated with tau-aggregate formation.
- In contrast, glycogen synthase kinase-3 activity (GSK-3 alpha beta) was reduced significantly.
- However, in schizophrenia brain, MAPK-phosphorylated tau was unchanged compared to matched controls, despite similar expression levels to those in AD.
Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The European journal of neuroscience) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 1 / 5 | 2004 — older than 20 years, still counted |
| 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15147305) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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