Elevated matrix metalloproteinase-9 levels in neuronal extracellular vesicles in Alzheimer's disease

Ann Clin Transl Neurol. 2020 Sep;7(9):1681-1691. doi: 10.1002/acn3.51155. Epub 2020 Aug 13.

Abstract

Objective: This study aimed to investigate plasma neuronally derived extracellular vesicle (NDEV) levels of core pathological markers [amyloid-β (Aβ) and phosphorylated tau] and inflammatory biomarkers, including interleukin 6 (IL-6) and matrix metalloproteinase-9 (MMP-9) in patients with Alzheimer's disease (AD).

Methods: Thirty-one patients with AD and 15 cognitively normal controls (NCs) were recruited. The diagnosis of AD was supported by fluorodeoxyglucose and Pittsburgh Compound-B PET scans. Plasma extracellular vesicles were extracted, precipitated, and enriched for neuronal source by anti-L1CAM antibody absorption. Levels of Aβ42, P-T181-tau, P-S396-tau, IL-6, and MMP-9 in plasma NDEVs were quantified by enzyme-linked immunosorbent assay (ELISA).

Results: Aβ42, P-T181-tau, and MMP-9 levels in plasma NDEVs were significantly higher in patients with AD than NCs. However, P-S396-tau and IL-6 levels in plasma NDEVs did not differ between AD patients and NCs. Moreover, there was no correlation between any of these biomarker levels and cognitive function as measured with Mini-Mental State Examination in patients with AD.

Conclusions: These findings provide further support that levels of core pathological markers, including Aβ42 and P-T181-tau, are elevated in plasma NDEVs of patients with AD. Furthermore, MMP-9 might play an important role in the pathogenesis of AD, and is a promising inflammatory biomarker for AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Amyloid beta-Peptides / metabolism
  • Biomarkers / blood
  • Extracellular Vesicles / metabolism*
  • Female
  • Humans
  • Interleukin-6 / metabolism
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Neurons / metabolism*
  • Peptide Fragments / metabolism
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • IL6 protein, human
  • Interleukin-6
  • MAPT protein, human
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins
  • MMP9 protein, human
  • Matrix Metalloproteinase 9

Grants and funding

This work was funded by Tianjin Binhai New District Social Development Science and Technology Project grant BHXQKJXM‐SF‐2018‐02; Tianjin Education Commission Scientific Research Project grants 2018KJ059 and 2018KJ060; National Nature Science Foundation of China grant 81870831.