PGC-1alpha expression decreases in the Alzheimer disease brain as a function of dementia
Qin W, Haroutunian V, Katsel P, Cardozo CP, Ho L, Buxbaum JD, Pasinetti GM.. Archives of neurology, 2009-03-01
Topic: Brain proteins, microglia and lab models
Objectives To explore mechanisms through which altered peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) expression may influence Alzheimer disease (AD) amyloid neuropathology and to test the hypothesis that promotion of PGC-1alpha expression in neurons might be developed as a novel therapeutic strategy in AD. Design Case-control. Patients Human postmortem brain (hippocampal formation) samples from AD cases and age-matched non-AD cases. Results Using genome-wide complementary DNA microarray analysis, we found that PGC-1alpha messenger RNA expression was significantly decreased as a function of progression of clinical dementia in the AD brain. Following confirmatory real-time polymerase chain reaction assay, we continued to explore the role of PGC-1alpha in clinical dementia and found that PGC-1alpha protein content was negatively associated with both AD-type neuritic plaque pathology and beta-amyloid (Abeta)(X-42) contents. Moreover, we found that the predicted elevation of amyloidogenic Abeta(1-42) and Abeta(1-40) peptide accumulation in embryonic cortico-hippocampal neurons derived from Tg2576 AD mice under hyperglycemic conditions (glucose level, 182-273 mg/dL) coincided with a dose-dependent attenuation in PGC-1alpha expression. Most importantly, we found that the reconstitution of exogenous PGC-1alpha expression in Tg2576 neurons attenuated the hyperglycemic-mediated beta-amyloidogenesis through mechanisms involving the promotion of the "nonamyloidogenic" alpha-secretase processing of amyloid precursor protein through the attenuation of the forkheadlike transcription factor 1 (FoxO3a) expression. Conclusion Therapeutic preservation of neuronal PGC-1alpha expression promotes the nonamyloidogenic processing of amyloid precursor protein precluding the generation of amyloidogenic Abeta peptides.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Qin, W., Haroutunian, V., Katsel, P., Cardozo, C. P., Ho, L., Buxbaum, J. D., et al. (2009). PGC-1alpha expression decreases in the Alzheimer disease brain as a function of dementia. Archives of neurology. https://doi.org/10.1001/archneurol.2008.588
Vancouver
Qin W, Haroutunian V, Katsel P, Cardozo CP, Ho L, Buxbaum JD, et al. PGC-1alpha expression decreases in the Alzheimer disease brain as a function of dementia. Archives of neurology. 2009. doi:10.1001/archneurol.2008.588. PMID: 19273754.
BibTeX
@article{qin2009-19273754,
author = {Qin, W. and Haroutunian, V. and Katsel, P. and Cardozo, C. P. and Ho, L. and Buxbaum, J. D. and Pasinetti, G. M.},
title = {{PGC-1alpha expression decreases in the Alzheimer disease brain as a function of dementia}},
journal = {Archives of neurology},
year = {2009},
doi = {10.1001/archneurol.2008.588},
pmid = {19273754},
url = {https://doi.org/10.1001/archneurol.2008.588}
}
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Results Using genome-wide complementary DNA microarray analysis, we found that PGC-1alpha messenger RNA expression was significantly decreased as a function of progression of clinical dementia in the AD brain.
- Following confirmatory real-time polymerase chain reaction assay, we continued to explore the role of PGC-1alpha in clinical dementia and found that PGC-1alpha protein content was negatively associated with both AD-type neuritic plaque pathology and beta-amyloid (Abeta)(X-42) contents.
- Moreover, we found that the predicted elevation of amyloidogenic Abeta(1-42) and Abeta(1-40) peptide accumulation in embryonic cortico-hippocampal neurons derived from Tg2576 AD mice under hyperglycemic conditions (glucose level, 182-273 mg/dL) coincided with a dose-dependent attenuation in PGC-1alpha expression.
- Most importantly, we found that the reconstitution of exogenous PGC-1alpha expression in Tg2576 neurons attenuated the hyperglycemic-mediated beta-amyloidogenesis through mechanisms involving the promotion of the "nonamyloidogenic" alpha-secretase processing of amyloid precursor protein through the attenuation of the forkheadlike transcription factor 1 (FoxO3a) expression.
Why it matters
In donated brain tissue (hippocampus) from people with and without Alzheimer's, levels of PGC-1alpha — a protein that switches on other genes — were lower the more advanced the person's dementia had been, and lower levels went with more amyloid plaque and amyloid-beta 42. In mouse nerve cells grown in a dish under high sugar, putting PGC-1alpha back reduced amyloid production, which led the authors to suggest protecting PGC-1alpha as a treatment idea. This is a postmortem link plus a lab-dish experiment; it has not been shown to treat or prevent Alzheimer's in people.
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Study details
- Study designcase-control study
- Evidence strengthModerate
Limitations
This is a postmortem, cross-sectional comparison of brain tissue, so it shows an association with dementia severity at death but cannot show whether declining PGC-1alpha causes worsening symptoms or is a downstream consequence of them.
How this study scored 53/100
Published in a peer-reviewed journal, and it is a case-control study. 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 (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (OpenAlex, 2026-10-29) |
| Study design | 6 / 12 | A case-control study |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2009 — within 20 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 | 6 / 7 | Cited 377 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 19.8 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 4 / 6 | Cited 9.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 2 / 4 | Cited 45 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Giulio Maria Pasinetti: h-index 83 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Icahn School of Medicine at Mount Sinai: institution h-index 1,331 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19273754) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 53 / 100 | — |
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Read the original
- DOI: 10.1001/archneurol.2008.588
- PubMed: 19273754
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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