Biomarkers.

Area of Science:

• Neuroscience
• Biochemistry
• Pathology

Background:

• Alzheimer's disease (AD) pathogenesis involves amyloid and cerebrovascular issues.
• Matrix metalloproteinases (MMPs) influence both amyloid-beta (Aβ) degradation and cerebrovascular pathology.
• The exact role of MMPs in AD remains unclear, necessitating further investigation.

Purpose of the Study:

• To investigate the relationships between cerebrospinal fluid (CSF) levels of MMPs and amyloid and cerebrovascular pathologies in AD.
• To clarify the specific roles of MMP2 and MMP9 in the context of AD progression.

Main Methods:

• Analysis of CSF samples from 299 participants (cognitively unimpaired, MCI, AD, non-AD) from the CANDI cohort.
• Measurement of CSF MMP2, MMP9, Aβ38, Aβ40, and Aβ42.
• Utilized structural MRI, AV45 PET scans, and fluid biomarkers (Qalb, CSF PDGFRβ) to assess pathologies.

Main Results:

• CSF MMP2 levels were significantly lower in MCI and AD patients compared to controls.
• Decreased MMP2, not MMP9, correlated with lower CSF Aβ levels and higher Aβ PET SUVR.
• CSF MMP2 and MMP9 positively correlated with cerebrovascular pathologies (WMH, CMB, lacunes, PVS, Qalb).
• Lower CSF MMP2 was associated with longitudinal brain atrophy.

Conclusions:

• MMPs are implicated in cerebrovascular damage.
• MMP2 appears to have a protective role against amyloid pathology in AD.
• Clinical use of MMP inhibitors in AD should account for MMP2's protective effects on amyloid pathology.