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Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry
Published on: March 7, 2019
Investigation of matrix metalloproteinases, MMP-2 and MMP-9, in plasma reveals a decrease of MMP-2 in Alzheimer's
Nastasia K-H Lim1, Victor L Villemagne, Cynthia P W Soon
1Department of Pathology, The University of Melbourne, Parkville Vic, Australia.
Abstract:
Pathological changes in the Alzheimer's disease (AD) brain include amyoid-β (Aβ) plaques, and neurofibrillary tangles, as well as neuronal death and synaptic loss. Matrix metalloproteinases MMP-2 and MMP-9 are known to degrade Aβ, and their expressions are increased in the AD brain, in particular in the astrocytes surrounding amyloid plaque. To investigate a possible association between plasma metalloproteinases and AD, we quantified MMP-2 and MMP-9 activities in the plasma of healthy controls (HC, n = 56), cases with mild cognitive impairment (MCI, n = 45), and AD (n = 50). All cases had previously been imaged with Pittsburgh compound B (PiB) and had a Mini-Mental Status Examination (MMSE) assessment. MMP-2 and MMP-9 activity was determined using gelatine-zymography. There was a significant 1.5-fold decrease in MMP-2 activity in the AD group compared to HC (p < 0.001) and a 1.4-fold decrease compared to MCI (p < 0.01). There was no difference in MMP-9 levels between the three groups. A positive correlation was identified between MMP-2 plasma activity and MMSE score (r = 0.16, p < 0.05), but there was no association with PiB. This is the first report of a change in MMP-2 activity in AD plasma and these findings may provide some insight into AD pathogenesis.
Insights
Plasma MMP-2 activity is significantly decreased in Alzheimer's disease (AD) patients. This reduction in matrix metalloproteinase-2 correlates with cognitive function, offering new insights into AD pathogenesis.
Area of Science:
- Neuroscience
- Biochemistry
Background:
- Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) plaques, neurofibrillary tangles, neuronal loss, and synaptic damage.
- Matrix metalloproteinases (MMPs), specifically MMP-2 and MMP-9, are known to degrade Aβ and are upregulated in the AD brain, particularly around amyloid plaques.
Purpose of the Study:
- To investigate the potential association between plasma levels of MMP-2 and MMP-9 and Alzheimer's disease.
- To explore the relationship between plasma MMP activity, cognitive status (MMSE), and amyloid burden (PiB imaging).
Main Methods:
- Quantified MMP-2 and MMP-9 activities in plasma from healthy controls (HC), mild cognitive impairment (MCI), and AD patients using gelatin-zymography.
- Assessed cognitive function using the Mini-Mental Status Examination (MMSE) and amyloid burden via Pittsburgh Compound B (PiB) imaging.
Main Results:
- A significant 1.5-fold decrease in plasma MMP-2 activity was observed in the AD group compared to HC (p < 0.001) and a 1.4-fold decrease compared to MCI (p < 0.01).
- No significant differences in MMP-9 levels were found between the three groups.
- Plasma MMP-2 activity showed a positive correlation with MMSE scores (r = 0.16, p < 0.05) but not with PiB uptake.
Conclusions:
- This study reports for the first time a decrease in plasma MMP-2 activity in Alzheimer's disease patients.
- Reduced MMP-2 activity may be linked to cognitive decline in AD and could offer insights into the disease's pathogenesis.
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