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Author Notes:

Dr. Yong Shen and Dr. Rena Li, Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL 34243, USA. yshen@rfdn.org (Yong Shen); rli@rfdn.org (Rena Li).

For authors' disclosures,see online publication.

Subjects:

Research Funding:

This study is supported by grants from the National Institute on Aging (NIH R01AG032441-01 to RL and R01AG025888 to YS; P50 AG025688 and P30 NS055077 to AL); Alzheimer’s Association (Zenith Award and IIRG-07-59510 to YS); the American Health Assistance Foundation (G2006-118 to RL); and the Katharina-Hardt-Foundation; Bad Homburg vor der Höhe, Germany (to HH).

QS is the recipient from China Scholarship Council of Natural Science, No.2011637095.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • Alzheimer's disease
  • biomarker
  • mild cognitive impairment
  • plasma
  • tumor necrosis factor converting enzyme
  • TUMOR-NECROSIS-FACTOR
  • AMYLOID PRECURSOR PROTEIN
  • ALPHA-CONVERTING-ENZYME
  • CEREBROSPINAL-FLUID
  • SECRETASE CLEAVAGE
  • BETA PRODUCTION
  • TNF RECEPTORS
  • ALPHA-1-ANTICHYMOTRYPSIN
  • INFLAMMATION
  • BIOMARKERS

Increased Plasma TACE Activity in Subjects with Mild Cognitive Impairment and Patients with Alzheimer's Disease

Tools:

Journal Title:

Journal of Alzheimer's Disease

Volume:

Volume 41, Number 3

Publisher:

, Pages 877-886

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Evidence suggests that the tumor necrosis factor receptor (TNFR)-signaling pathway contributes to the pathogenesis of Alzheimer's disease (AD). TNF-α converting enzyme (TACE/ADAM-17) can cleave both pro-TNF-α and TNF receptors. Recently, we have shown that TACE activity in the cerebrospinal fluid (CSF) of subjects with mild cognitive impairment (MCI) and AD patients is significantly higher than that of cognitively healthy controls (HC). To date, it is not clear whether TACE activity could be detected in the human plasma and whether TACE activity in MCI and AD patients is different from that in HC. We analyzed TACE expression and activity in a large clinical sample of 64 patients with AD, 88 subjects with MCI, and 50 age-matched HC recruited from two distinct academic centers. Plasma TACE protein levels did not differ significantly in the three study groups (AD, MCI, and HC). However, plasma TACE activity in subjects with MCI and AD patients was significantly higher than that in HC. Moreover, in MCI and AD groups, we found a significant correlation between plasma TACE activity and CSF t-tau and Aβ42 levels and CSF Aβ42/tau ratios. In AD patients, the levels of plasma TACE activity correlated significantly and negatively with cognition. These findings further support the role of the TNF-α receptor complex in AD-related neuroinflammation and propose TACE plasma activity as a promising hypothesis-driven biomarker candidate for detection, diagnosis, and prognosis of prodromal and clinical AD.

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© 2014 – IOS Press and the authors. All rights reserved

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