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Increased matrix metalloproteinase 9 activity in mild cognitive impairment
Bruno MA, Mufson EJ, Wuu J, Cuello AC.. Journal of neuropathology and experimental neurology, 2009-12-01
Topic: Brain proteins, microglia and lab models
Nerve growth factor (NGF)-dependent cholinergic basal forebrain neurons degenerate during the progression of Alzheimer disease (AD). Elevated proNGF and reduced levels of the TrkA high-affinity NGF receptor occur in prodromal and advanced stages of AD. We recently described a protease cascade responsible for the conversion of proNGF to mature NGF (mNGF) in which matrix metalloproteinase 9 (MMP-9) degrades mNGF in the extracellular space. To determine whether this proteolytic cascade is altered during the progression of AD, we examined human frontal and parietal cortex tissues from aged subjects with a clinical diagnosis of AD, mild cognitive impairment, or no cognitive impairment. The analysis demonstrated greater MMP-9 activity in both AD and mild cognitive impairment compared with no cognitive impairment brain samples (p < 0.01), which supports the notion that a metabolic failure in the NGF-maturation/degradation pathway may be associated with an exacerbated degradation of mNGF in the cerebral cortex in early AD. Moreover, there were inverse correlations between Global Cognitive Score and Mini-Mental State Examination score and MMP-9 activity. These findings suggest that a reduction in mNGF as a consequence of MMP-9-mediated degradation may in part underlie the pathogenesis of cognitive deficits in mild cognitive impairment and AD.
Key findings
- The analysis demonstrated greater MMP-9 activity in both AD and mild cognitive impairment compared with no cognitive impairment brain samples (p < 0.01), which supports the notion that a metabolic failure in the NGF-maturation/degradation pathway may be associated with an exacerbated degradation of mNGF in the cerebral cortex in early AD.
- These findings suggest that a reduction in mNGF as a consequence of MMP-9-mediated degradation may in part underlie the pathogenesis of cognitive deficits in mild cognitive impairment and AD.
Why it matters
Higher MMP-9 activity was found in brain tissue from people with mild cognitive impairment and Alzheimer's disease compared with those with no cognitive impairment. This suggests that reduced mature nerve growth factor from MMP-9 degradation may contribute to the cognitive deficits seen in these conditions, though the study examined tissue samples and does not establish cause or a treatment.
Study details
- Evidence strengthLow
How this study scored 43/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neuropathology and experimental neurology) |
| Journal's citation record | 2 / 4 | Journal of Neuropathology & Experimental Neurology: journal h-index 239 (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 | 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 | 5 / 7 | Cited 162 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.5 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 3 / 6 | Cited 4.9× 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 | 2 / 4 | Cited 30 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author A. Claudio Cuello: h-index 100 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | McGill University: institution h-index 1,373 (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 19915485) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1097/nen.0b013e3181c22569
- PubMed: 19915485
- Original source →
- Free full text: PubMed Central →
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. Check the citation against the original before you use it.
APA 7th
Bruno, M. A., Mufson, E. J., Wuu, J., & Cuello, A. C. (2009). Increased matrix metalloproteinase 9 activity in mild cognitive impairment. Journal of neuropathology and experimental neurology. https://doi.org/10.1097/nen.0b013e3181c22569
Vancouver
Bruno MA, Mufson EJ, Wuu J, Cuello AC. Increased matrix metalloproteinase 9 activity in mild cognitive impairment. Journal of neuropathology and experimental neurology. 2009. doi:10.1097/nen.0b013e3181c22569. PMID: 19915485.
BibTeX
@article{bruno2009-19915485,
author = {Bruno, M. A. and Mufson, E. J. and Wuu, J. and Cuello, A. C.},
title = {{Increased matrix metalloproteinase 9 activity in mild cognitive impairment}},
journal = {Journal of neuropathology and experimental neurology},
year = {2009},
doi = {10.1097/nen.0b013e3181c22569},
pmid = {19915485},
url = {https://doi.org/10.1097/nen.0b013e3181c22569}
}
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