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Matrix Metalloproteinases in Alzheimer's Disease and Concurrent Cerebral Microbleeds
Flora H Duits, Mar Hernandez-Guillamon, Joan Montaner, Jereon D C Goos, Alex Montañola, Mike P Wattjes, Frederik Barkhof, Philip Scheltens et al.. Journal of Alzheimer's disease : JAD, 2015
Topic: Plasma and spinal-fluid biomarkers
Matrix metalloproteinases (MMPs) are a family of enzymes able to degrade components of the extracellular matrix, which is important for normal blood-brain barrier function. Their function is regulated by tissue inhibitors of matrix metalloproteinases (TIMPs). We investigated whether MMPs and TIMPs in cerebrospinal fluid (CSF) and plasma were altered in Alzheimer's disease (AD) and vascular dementia (VaD), and whether this effect was modified by presence of cerebral micro-bleeds in AD patients. In addition, we assessed associations of MMPs and TIMPs with CSF amyloid-β(1-42) (Aβ42), tau, and tau phosphorylated at threonine-181 (p-tau). We measured MMP2, MMP9, and MMP10, and TIMP1 and TIMP2 in CSF and plasma of 52 AD patients, 26 matched controls, and 24 VaD patients. AD patients showed higher plasma MMP2 levels compared to VaD patients (p < 0.05), and higher CSF MMP10 levels compared to controls (p < 0.05). Microbleeds in AD were associated with lower CSF TIMP1, TIMP2 and MMP9 in a dose-response relation. In addition, CSF MMP2 was associated with p-tau (St.B 0.23, p < 0.05), and CSF MMP10 with tau (St.B 0.38, p < 0.001) and p-tau (St.B 0.40, p < 0.001). Our findings suggest involvement of MMP2 and MMP10 in AD pathology. Lower levels of TIMPs in AD patients with microbleeds suggest less MMP inhibition in patients with concurrent cerebral microbleeds, which may hypothetically lead to a more vulnerable blood-brain barrier in these patients.
Key findings
- AD patients showed higher plasma MMP2 levels compared to VaD patients (p < 0.05), and higher CSF MMP10 levels compared to controls (p < 0.05).
- Microbleeds in AD were associated with lower CSF TIMP1, TIMP2 and MMP9 in a dose-response relation.
- In addition, CSF MMP2 was associated with p-tau (St.B 0.23, p < 0.05), and CSF MMP10 with tau (St.B 0.38, p < 0.001) and p-tau (St.B 0.40, p < 0.001).
- Our findings suggest involvement of MMP2 and MMP10 in AD pathology.
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Study details
- Evidence strengthLow
How this study scored 38/100
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, multi-centre collaboration and free to read, so those were left out: it earned 21 of the 56 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer's disease : JAD) |
| 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 | 2015 — 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 | — / 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 26402072) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 21 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 21 of the 56 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
What each of these 20 components measures, and what this score is not →
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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
Duits, F. H., Hernandez-Guillamon, M., Montaner, J., Goos, J. D. C., Montañola, A., Wattjes, M. P., et al. (2015). Matrix Metalloproteinases in Alzheimer's Disease and Concurrent Cerebral Microbleeds. Journal of Alzheimer's disease : JAD. https://doi.org/10.3233/jad-143186
Vancouver
Duits FH, Hernandez-Guillamon M, Montaner J, Goos JDC, Montañola A, Wattjes MP, et al. Matrix Metalloproteinases in Alzheimer's Disease and Concurrent Cerebral Microbleeds. Journal of Alzheimer's disease : JAD. 2015. doi:10.3233/jad-143186. PMID: 26402072.
BibTeX
@article{duits2015-26402072,
author = {Duits, Flora H and Hernandez-Guillamon, Mar and Montaner, Joan and Goos, Jereon D C and Montañola, Alex and Wattjes, Mike P and Barkhof, Frederik and Scheltens, Philip and others},
title = {{Matrix Metalloproteinases in Alzheimer's Disease and Concurrent Cerebral Microbleeds}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2015},
doi = {10.3233/jad-143186},
pmid = {26402072},
url = {https://doi.org/10.3233/jad-143186}
}
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