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Relationship between Cerebrospinal Fluid Matrix Metalloproteinases Levels and Brain Amyloid Deposition in Mild

Yuuki Sasaki1, Noriyuki Kimura1, Yasuhiro Aso1

  • 1Department of Neurology, Faculty of Medicine, Oita University, Oita 879-5593, Japan.

Biomolecules
|October 23, 2021
PubMed

Insights

Cerebrospinal fluid (CSF) matrix metalloproteinases (MMPs) are linked to brain amyloid deposition and white matter lesion severity in mild cognitive impairment (MCI). Specifically, MMP-2 correlates with amyloid, while MMP-7 relates to lesion severity.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Medical Imaging

Background:

  • Mild cognitive impairment (MCI) is a prodromal stage of dementia, characterized by cognitive decline.
  • Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play roles in extracellular matrix remodeling and have been implicated in neurodegenerative diseases.
  • Understanding the relationship between MMPs/TIMPs and neuropathological hallmarks in MCI is crucial for early diagnosis and intervention.

Purpose of the Study:

  • To investigate the association between cerebrospinal fluid (CSF) levels of MMPs and TIMPs with brain amyloid deposition, glucose metabolism, and white matter lesions (WMLs) in amnestic MCI.
  • To explore the potential role of specific MMPs in the early stages of Alzheimer's disease pathogenesis.

Main Methods:

  • Study included 33 individuals with amnestic MCI.
  • Utilized 11C-Pittsburgh compound B positron emission tomography (PiB-PET) for amyloid imaging.
  • Employed 18F-fluorodeoxyglucose positron emission tomography for glucose metabolism assessment.
  • Assessed white matter lesions (WMLs) using MRI/CT and the Fazekas scale.
  • Measured CSF levels of MMPs and TIMPs via multiplex assays.

Main Results:

  • CSF MMP-2 levels showed a negative correlation with global PiB uptake, particularly in the parietotemporal lobe and posterior cingulate gyrus.
  • CSF MMP-7 levels were positively correlated with the severity of white matter lesions (WMLs).
  • No significant associations were found for other MMPs or TIMPs with the studied biomarkers.

Conclusions:

  • CSF MMP-2 levels are associated with brain amyloid deposition in individuals with amnestic MCI.
  • CSF MMP-7 levels are linked to the severity of white matter lesions in this cohort.
  • These findings suggest a role for MMPs in amyloid-beta catabolism and blood-brain barrier integrity during the MCI stage.
Keywords:
11C-Pittsburgh compound B positron emission tomography18F-fluorodeoxyglucose positron emission tomographycerebrospinal fluidmatrix metalloproteinasesmild cognitive impairmenttissue inhibitor of metalloproteinaseswhite matter lesions

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