The DOI matches its Crossref record; 45 of the 46 references it cites were found in a registry or an index.
Matrix metalloproteinase-9 (MMP-9) is synthesized in neurons of the human hippocampus and is capable of degrading the amyloid-β peptide (1–40).
Open accessAbstract
We reported earlier that the levels of Ca 2+ -dependent metalloproteinases are increased in Alzheimer’s disease (AD) specimens, relative to control specimens. Here we show that these enzymes are forms of the matrix metalloproteinase MMP-9 (EC 3.4.24.35 ) and are expressed in the human hippocampus. Affinity-purified antibodies to MMP-9 labeled pyramidal neurons, but not granular neurons or glial cells. MMP-9 mRNA is expressed in pyramidal neurons, as determined with digoxigenin-labeled MMP-9 riboprobes, and the presence of this mRNA is confirmed with reverse transcriptase PCR. The cellular distribution of MMP-9 is altered in AD because 76% of the total 100 kDa enzyme activity is found in the soluble fraction of control specimens, whereas only 51% is detectable in the same fraction from AD specimens. The accumulated 100 kDa enzyme from AD brain is latent and can be converted to an active form with aminophenylmercuric acetate. MMP-9 also is detected in close proximity to extracellular amyloid plaques. Because a major constituent of plaques is the 4 kDa β-amyloid peptide, synthetic Aβ 1–40 was incubated with activated MMP-9. The enzyme cleaves the peptide at several sites, predominantly at Leu 34 -Met 35 within the membrane-spanning domain. These results establish that neurons have the capacity to synthesize MMP-9, which, on activation, may degrade extracellular substrates such as β-amyloid. Because the latent form of MMP-9 accumulates in AD brain, it is hypothesized that the lack of enzyme activation contributes to the accumulation of insoluble β-amyloid peptides in plaques.
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“Increasing in vitro evidence indicates that some MMPs may play an important role in degrading soluble Ab (sAb), such as secreted MMP-2 and MMP-9 that generate C-terminally truncated Ab fragments and membrane-type MMP-14 that degrades both soluble and fibrillary Ab (29)(30)(31)(32).”
From Differential protective effects of connective tissue growth factor against Aβ neurotoxicity on neurons and glia (2017) · cites this paper as [29]
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In the citing paper
“MMP-9 is capable of cleaving Aβ in vitro (Backstrom et al., 1996)”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Backstrom et al., 1996
In the citing paper
“In parallel, a number of these CNS diseases exhibit dysregulated expression of enzymes necessary for PNN cleavage and reorganization (Backstrom et al., 1996; Lorenzl et al., 2003; Rybakowski et al., 2009; Kim et al., 2009; Zhang et al., 2011; Yamamori et al., 2013; Liu et al., 2014; Rankin-Gee et al., 2015; Lepeta et al., 2017).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Backstrom et al., 1996
In the citing paper
“plasma levels of MMP-9 are elevated in AD patients (Backstrom et al., 1996; Lorenzl et al., 2003).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Backstrom et al., 1996
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Ning, M., Montaner, J., Wang, X., Lee, S. ‐., Tsuji, K., Tejima, E., Buchan, A. M., & Lo, E. H. (2006) · Springer eBooks · doi:10.1007/978-0-387-30383-3_15
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Wallin, A., & Bjerke, M. (2014) · Cambridge University Press eBooks · doi:10.1017/cbo9781139382694.018
Bannikov, G. A., Collier, I. E., & Goldberg, G. I. (2004) · Elsevier eBooks · doi:10.1016/b978-0-12-079611-3.50138-5
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Jäkel, L., Kuiperij, H. B., Gerding, L. P., Custers, E., van den Berg, E., Jolink, W. M. T., Schreuder, F. H. B. M., Küsters, B., Klijn, C. J. M., & Verbeek, M. M. (2020) · Figshare · doi:10.6084/m9.figshare.12617913
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Rôle des ADAM dans le processus physiopathologique de la maladie d'Alzheimer
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Etude de l'interaction du TIMP-1 avec ses récepteurs
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Ketogenic diet impacts Blood-Brain Barrier physiology : implications for Alzheimers's disease
Corsi, M. (2018) · theses.fr (ABES) · doi:10.70675/36cd4c36z2faaz4535zaafdz8f54069c5015
Molecular mechanisms of action of MT-MMPs involved in the pathogenesis of Alzheimer’s disease
García‐González, L. (2020) · theses.fr (ABES) · doi:10.70675/a04672c0z1f4az472ezbcd5zbea446eac50c
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Frank, M., Barthélémy, C., Dufour, A., Rivera, S., & Baranger, K. (2026) · The Enzymes · doi:10.1016/bs.enz.2026.07.004
Correlation between MMP-3-1171 5A/6A polymorphism and the risk of Alzheimer’s disease
Wang, Y., Zhu, S., Ma, Y., Chen, X., & Zhou, M. (2026) · Medicine · doi:10.1097/md.0000000000050560
“[5–7] Recent animal and post-mortem studies indicate that MMPs that are involved in the degradation of connective tissue and extracellular matrix are implicated in the pathogenesis of AD.”
Johnson, A. K., Hulle, C. A. V., Zylstra, H., Cronin, K. A., Johnson, K., Rivera‐Rivera, L. A., Chappell, R., Wilson, R., Kac, P. R., Gleason, C. E., et al. (2026) · Neurobiology of Disease · doi:10.1016/j.nbd.2026.107605
“Importantly, MMP-9 not only interacts with CX3CL1, but it also has been reported to be expressed within the human brain tissue (Backstrom et al., 1996; Li et al., 2026) and can function to cleave amyloid-beta and tau protein (Backstrom et al., 1996; Nübling et al., 2012).”
The role of matrix metalloproteinases in Alzheimer's disease and small vessel disease
Nguyen, N., Huynh, S., Mroczko, B., & Glodzik, L. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261494579
Metadata
- Authors
- Backstrom, J. R., Lim, G. P., Cullen, M. J., & Tökés, Z. A.
- Affiliations
- University of Southern California (US)
- ORCID
- Cullen, Michael J.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1996-12-15
- Volume
- 16
- Issue
- 24
- Pages
- 7910-7919
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W4296941341
- Cited by
- 331
- References
- 46
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 9 · 2023: 6 · 2022: 10 · 2021: 16 · 2020: 21 · 2019: 5 · 2018: 13 · 2017: 15 · 2016: 11 · 2015: 18 · 2014: 18 · 2013: 8 · 2012: 12
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Funders
- National Institute on Aging (R01-AG09681)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- MMP-9, Alzheimer's disease, Aβ40, hippocampal pyramidal neurons, MMP-9 mRNA expression, extracellular matrix metalloproteinases, transmembrane domain
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