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Proteomics and Protein Markers |
1 Innogenetics NV, Gent, Belgium.
2 Neurotec, Department of Geriatric Medicine, Huddinge University Hospital, Stockholm, Sweden.
3 Department of Clinical Neuroscience, Department of Psychiatry, Göteborg University, Mölndal, Sweden.
4 Department of Clinical Neuroscience, Experimental Neuroscience, Sahlgrenska University Hospital, Mölndal, Sweden.
aAddress correspondence to this author at: Industriepark Zwijnaarde 7, Box 4, B-9052 Gent, Belgium. Fax 32-9-241-0907; e-mail hugovdr{at}innogenetics.be.
Background: Early identification of patients with mild cognitive impairment (MCI) progressing to Alzheimer disease (MCI-AD) by use of biomarkers in cerebrospinal fluid (CSF) is an essential step toward improving clinical diagnosis and drug development. We evaluated whether different ß-amyloid42 (Aß42) peptides can add further information to the combined use of tau and Aß1–42 for predicting risk of progression of MCI to AD.
Methods: We used xMAP® technology to simultaneously quantify different Aß42 peptides modified at the amino terminus, tau, and phosphorylated tau (P-tau181P) in CSF. Aß42 peptide concentrations were measured by use of immunoreactivity toward Aß monoclonal antibodies [3D6 (Aß42-3D6), WO2 (Aß42-WO2), 6E10 (Aß42-6E10), and 4G8 (Aß42-4G8)]. The discriminant ability of the markers was evaluated by ROC curve analysis.
Results: The areas under the curves for the separation of MCI-AD from nonprogressing MCI (MCI-N) were significantly higher when we used Aß42-3D6/Aß42-WO2, Aß42-3D6/Aß42-6E10, or Aß42-3D6/Aß42-4G8 compared with Aß42-3D6. In addition, differentiation of MCI-N from MCI-AD was improved by quantification of full-length Aß1–42 (Aß42-3D6) compared with Aß42-WO2, Aß42-6E10, or Aß42-4G8. Several Aß42 peptides truncated at the amino terminus (Aß11–42 and Aß8–42) were identified in CSF by surface-enhanced laser desorption/ionization time-of-flight technology.
Conclusion: The CSF markers tau, Aß42 forms, and P-tau181P, when used as adjuncts to clinical diagnosis, have the potential to help identify AD pathology and could be a valuable asset for early AD diagnosis.
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