Increased matrix metalloproteinase 9 activity in mild cognitive impairment

Area of Science:

• Neuroscience
• Biochemistry

Background:

• Cholinergic basal forebrain neurons, dependent on nerve growth factor (NGF), degenerate in Alzheimer disease (AD).
• Elevated proNGF and reduced TrkA receptor levels are observed in prodromal and advanced AD stages.
• A protease cascade involving matrix metalloproteinase 9 (MMP-9) degrades mature NGF (mNGF).

Purpose of the Study:

• To investigate alterations in the NGF proteolytic cascade during AD progression.
• To examine the role of MMP-9 in NGF degradation in human brain tissues across cognitive statuses.

Main Methods:

• Analysis of human frontal and parietal cortex tissues from individuals with AD, mild cognitive impairment (MCI), and no cognitive impairment (NCI).
• Assay of matrix metalloproteinase 9 (MMP-9) activity.
• Correlation analysis with Global Cognitive Score and Mini-Mental State Examination (MMSE) scores.

Main Results:

• MMP-9 activity was significantly greater in both AD and MCI brain samples compared to NCI samples (p < 0.01).
• Inverse correlations were found between cognitive scores (Global Cognitive Score, MMSE) and MMP-9 activity.
• These findings suggest a link between increased MMP-9 and reduced mNGF in early AD stages.

Conclusions:

• A metabolic failure in NGF maturation/degradation, specifically exacerbated mNGF degradation by MMP-9, is associated with early AD.
• Reduced mNGF levels due to MMP-9 activity may contribute to the pathogenesis of cognitive deficits in MCI and AD.