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Proteomic and functional analyses reveal a mitochondrial dysfunction in P301L tau transgenic mice
David DC, Hauptmann S, Scherping I, Schuessel K, Keil U, Rizzu P, Ravid R, Dröse S et al.. The Journal of biological chemistry, 2005-04-14
Topic: Brain proteins, microglia and lab models
Transgenic mice overexpressing the P301L mutant human tau protein exhibit an accumulation of hyperphosphorylated tau and develop neurofibrillary tangles. The consequences of tau pathology were investigated here by proteomics followed by functional analysis. Mainly metabolism-related proteins including mitochondrial respiratory chain complex components, antioxidant enzymes, and synaptic proteins were identified as modified in the proteome pattern of P301L tau mice. Significantly, the reduction in mitochondrial complex V levels in the P301L tau mice revealed using proteomics was also confirmed as decreased in human P301L FTDP-17 (frontotemporal dementia with parkinsonism linked to chromosome 17) brains. Functional analysis demonstrated a mitochondrial dysfunction in P301L tau mice together with reduced NADH-ubiquinone oxidoreductase activity and, with age, impaired mitochondrial respiration and ATP synthesis. Mitochondrial dys-function was associated with higher levels of reactive oxygen species in aged transgenic mice. Increased tau pathology as in aged homozygous P301L tau mice revealed modified lipid peroxidation levels and the up-regulation of antioxidant enzymes in response to oxidative stress. Furthermore, P301L tau mitochondria displayed increased vulnerability toward beta-amyloid (Abeta) peptide insult, suggesting a synergistic action of tau and Abeta pathology on the mitochondria. Taken together, we conclude that tau pathology involves a mitochondrial and oxidative stress disorder possibly distinct from that caused by Abeta.
Key findings
- Significantly, the reduction in mitochondrial complex V levels in the P301L tau mice revealed using proteomics was also confirmed as decreased in human P301L FTDP-17 (frontotemporal dementia with parkinsonism linked to chromosome 17) brains.
- Functional analysis demonstrated a mitochondrial dysfunction in P301L tau mice together with reduced NADH-ubiquinone oxidoreductase activity and, with age, impaired mitochondrial respiration and ATP synthesis.
- Mitochondrial dys-function was associated with higher levels of reactive oxygen species in aged transgenic mice.
- Increased tau pathology as in aged homozygous P301L tau mice revealed modified lipid peroxidation levels and the up-regulation of antioxidant enzymes in response to oxidative stress.
- Taken together, we conclude that tau pathology involves a mitochondrial and oxidative stress disorder possibly distinct from that caused by Abeta.
Why it matters
In P301L tau transgenic mice, this work found mitochondrial dysfunction, reduced complex V levels, impaired respiration and ATP synthesis, and greater vulnerability to beta-amyloid. It is animal research, so it does not yet show any treatment, cure or prevention for Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 49/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of biological chemistry) |
| Journal's citation record | 4 / 4 | Journal of Biological Chemistry: journal h-index 780 (OpenAlex, 2026-10-29) |
| 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 | 2005 — 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 | Laboratory or animal study (title names “transgenic”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 449 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 19.5 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 4 / 6 | Cited 10.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 3 / 4 | Cited 57 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Jürgen Götz: h-index 88 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Zurich: institution h-index 1,220 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15831501) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 49 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1074/jbc.m500356200
- PubMed: 15831501
- Original source →
- Free full text: Journal of Biological Chemistry →
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
David, D. C., Hauptmann, S., Scherping, I., Schuessel, K., Keil, U., Rizzu, P., et al. (2005). Proteomic and functional analyses reveal a mitochondrial dysfunction in P301L tau transgenic mice. The Journal of biological chemistry. https://doi.org/10.1074/jbc.m500356200
Vancouver
David DC, Hauptmann S, Scherping I, Schuessel K, Keil U, Rizzu P, et al. Proteomic and functional analyses reveal a mitochondrial dysfunction in P301L tau transgenic mice. The Journal of biological chemistry. 2005. doi:10.1074/jbc.m500356200. PMID: 15831501.
BibTeX
@article{david2005-15831501,
author = {David, D. C. and Hauptmann, S. and Scherping, I. and Schuessel, K. and Keil, U. and Rizzu, P. and Ravid, R. and Dröse, S. and others},
title = {{Proteomic and functional analyses reveal a mitochondrial dysfunction in P301L tau transgenic mice}},
journal = {The Journal of biological chemistry},
year = {2005},
doi = {10.1074/jbc.m500356200},
pmid = {15831501},
url = {https://doi.org/10.1074/jbc.m500356200}
}
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