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Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry
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Matrix metalloproteinase-β19 expressed in cerebral amyloid angiopathy

Maarit Tanskanen1, Liisa Myllykangas, Ulpu Saarialho-Kere

  • 1Department of Pathology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. maarit.tanskanen@helsinki.fi

Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis
|January 26, 2011
PubMed
Abstract

Insights

Matrix metalloproteinase-19 (MMP-19) is found in the blood vessels of individuals with cerebral amyloid angiopathy (CAA), suggesting a role for MMPs in this condition and associated hemorrhages.

Area of Science:

  • Neuropathology
  • Molecular Biology
  • Vascular Biology

Background:

  • Cerebral amyloid angiopathy (CAA) is common in Alzheimer's disease (AD) and can lead to CAA-associated intracerebral hemorrhage (CAAH).
  • Matrix metalloproteinases (MMPs) have been implicated in CAA and hemorrhage in previous studies.
  • The specific role of MMPs in human CAA and CAAH requires further investigation.

Purpose of the Study:

  • To investigate the expression and localization of specific MMPs in human cerebral amyloid angiopathy (CAA) and CAA-associated intracerebral hemorrhage (CAAH).
  • To determine the association between MMP expression and the presence of CAA and intracerebral hemorrhage.

Main Methods:

  • Immunohistochemistry (IHC) was used to detect MMP-1, -2, -7, -9, -19, and -26 expression.
  • Tissue microarrays (TMAs) from individuals with AD, CAAH, and controls were analyzed (Step 1).
  • Findings were confirmed in a larger cohort of individuals with and without CAA and hemorrhage (Step 2).

Main Results:

  • Vascular immunoreactivity for MMP-19 and MMP-26 was detected in cerebral blood vessels in CAA.
  • MMP-19 expression in blood vessels was significantly associated with both CAA and intracerebral hemorrhage.
  • Multivariate analysis indicated that the association between vascular MMP-19 and hemorrhage was dependent on the presence of CAA.

Conclusions:

  • This study provides the first human evidence of MMP-19 immunoreactivity in amyloid-laden blood vessels in CAA.
  • These findings suggest a potential role for MMP-19 in the pathogenesis of CAA and associated hemorrhages.
  • Further research into MMPs' involvement in CAA is warranted.

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