title: Increased plasma TACE activity in subjects with mild cognitive impairment and patients with Alzheimer's disease.
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.
authors.affiliation: Center for Advanced Therapeutic Strategies for Brain Disorders, The Roskamp Institute, Sarasota, FL, USA Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Qiying
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Psychiatry and Psychotherapy, Alzheimer Memorial Center, University of Munich, Munich, Germany Université Pierre et Marie Curie, Département de Neurologie, Institut de la Mémoire et de la Maladie d'Alzheimer, Hôpital de la Salpêtrière, Paris, France.
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
authors.affiliation: Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Sahlgren's University Hospital, Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Université Pierre et Marie Curie, Département de Neurologie, Institut de la Mémoire et de la Maladie d'Alzheimer, Hôpital de la Salpêtrière, Paris, France.
authors.forename: Simone
authors.initials: S
authors.lastname: Lista
authors.affiliation: Department of Neurology and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Levey
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Beisha
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, China Center for Hormone Advanced Science and Education, Roskamp Institute, Sarasota, FL, USA.
authors.forename: Rena
authors.initials: R
authors.lastname: Li
authors.affiliation: Center for Advanced Therapeutic Strategies for Brain Disorders, The Roskamp Institute, Sarasota, FL, USA Department of Neurology, Xiangya Hospital, Central South University, Changsha, China Department of Neurology, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Shen
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000072198:ADAM17 Protein; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D060825:Cognitive Dysfunction / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
keywords: Alzheimer's disease; biomarker; mild cognitive impairment; plasma; tumor necrosis factor converting enzyme