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Updated: Aug 7, 2026
Detection of Neuritic Plaques in Alzheimer's Disease Mouse Model
Published on: July 26, 2011
Matrix metalloproteinases in dog brains exhibiting Alzheimer-like characteristics
G P Lim1, M J Russell, M J Cullen
1Department of Cell and Neurobiology, School of Medicine, University of Southern California, Los Angeles 90033, USA.
Abstract:
We have previously reported that the amount of the neuronal matrix metalloproteinase (MMP) MMP-9, capable of cleaving beta-amyloid,-40 predominantly at Leu34-Met35, is increased in a latent form in hippocampal specimens from AD patients and have suggested that the lack of activation of this enzyme may contribute to the deposition of beta-amyloid in plaques. The current study addresses whether similar matrix proteinases are detectable in amyloid-positive and -negative brain specimens of aged beagles. Using quantitative zymography, three major neutral proteinases with molecular masses of 60, 95, and 280 kDa were readily detected. These enzymes have the characteristics of MMPs because they were inhibited by EDTA and 1, 10-phenanthroline, and their activities were restored by addition of both Ca2+ and Zn2+. The 95- and 280-kDa proteinases cross-reacted with specific monoclonal antibodies to human MMP-9 (gelatinase B; EC 3.4. 24.35). Canine MMP-9 was latent because activation by organomercurial treatment resulted in a characteristic decrease in molecular mass. Statistical analysis revealed no difference in the 60-kDa proteinase activity in amyloid-positive and -negative brain specimens. However, significantly increased amounts of latent MMP-9 were observed in amyloid-positive brain specimens (p < or = 0.05) compared with amyloid-negative brain specimens. The observations document that changes in MMP-9 expression in amyloid-positive beagle brains are similar to those reported in the human Alzheimer's disease hippocampus and suggest the possibility that insufficient activation of MMP-9 may contribute to beta-amyloid accumulation, a hypothesis that needs to be further investigated.
Insights
Increased latent matrix metalloproteinase-9 (MMP-9) was found in amyloid-positive beagle brains, similar to Alzheimer
Area of Science:
- Neuroscience
- Biochemistry
- Enzymology
Background:
- Neuronal matrix metalloproteinase (MMP)-9 cleaves beta-amyloid and is elevated in Alzheimer's disease (AD) hippocampus.
- Latent MMP-9 in AD may contribute to beta-amyloid plaque deposition.
- This study investigates MMPs in aged beagle brains with and without amyloid plaques.
Purpose of the Study:
- To determine if matrix proteinases similar to those in human AD are present in aged beagle brains.
- To compare the levels of these proteinases in amyloid-positive versus amyloid-negative beagle brain specimens.
- To investigate the role of MMP-9 activation in beta-amyloid accumulation.
Main Methods:
- Quantitative zymography to detect and characterize neutral proteinases in brain specimens.
- Inhibition assays using EDTA and 1,10-phenanthroline to confirm metalloproteinase activity.
- Cross-reactivity with monoclonal antibodies to human MMP-9 to identify specific enzymes.
- Organomercurial treatment to assess the latency of canine MMP-9.
- Statistical analysis to compare proteinase levels between amyloid-positive and -negative groups.
Main Results:
- Three major neutral proteinases (60, 95, 280 kDa) with metalloproteinase characteristics were detected.
- The 95- and 280-kDa proteinases were identified as MMP-9.
- Canine MMP-9 was found in a latent form, with activity restored upon activation.
- No significant difference in 60-kDa proteinase activity was observed between groups.
- Significantly higher levels of latent MMP-9 were found in amyloid-positive beagle brains compared to amyloid-negative brains (p < 0.05).
Conclusions:
- Changes in MMP-9 expression in amyloid-positive beagle brains mirror those in human AD hippocampus.
- Elevated latent MMP-9 in amyloid-positive brains suggests a potential role in beta-amyloid accumulation.
- Insufficient MMP-9 activation is a plausible hypothesis for beta-amyloid deposition that warrants further investigation.
