Elevated matrix metalloproteinase‐9 levels in neuronal extracellular vesicles in Alzheimer’s disease

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.