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Golgin A4 in CSF and granulovacuolar degenerations of patients with Alzheimer disease

Item Type:Article
Title:Golgin A4 in CSF and granulovacuolar degenerations of patients with Alzheimer disease
Creators Name:Kork, F. and Jankowski, J. and Goswami, A. and Weis, J. and Brook, G. and Yamoah, A. and Anink, J. and Aronica, E. and Fritz, S. and Huck, C. and Schipke, C. and Peters, O. and Tepel, M. and Noels, H. and Jankowski, V.
Abstract:OBJECTIVE: To isolate and identify a new, as yet unknown molecule in CSF that could serve as marker for Alzheimer disease. METHODS: We immunized mice with human CSF and fused hybridomas for monoclonal antibodies and screened these antibodies for their capacity to discriminate CSF of patients with Alzheimer disease from CSF of controls. We then chromatographically isolated the antigen to the best discriminating antibody and identified the antigen using mass spectrometric methods. Thereafter, we quantified the CSF concentration of the antigen in a new cohort of patients with Alzheimer disease and controls and performed immunohistochemistry of postmortem brain tissue derived from patients with Alzheimer disease and controls. RESULTS: We generated >200 hybridomas and selected 1 antibody that discriminated CSF from patients with Alzheimer disease from that of controls. We identified golgin A4 as the antigen detected by this antibody. Golgin A4 concentration was significantly higher in CSF from patients with Alzheimer disease than in CSF of controls (145 [interquartile range 125–155] vs 115 [ 99–128] pg/mL, p < 0.001) and demonstrated a substantial discriminative power (area under the receiver operating characteristic curve 0.80, 95% confidence interval 0.67–0.94). Immunohistochemistry of postmortem brain sections from patients with Alzheimer disease revealed a significant accumulation of golgin A4 in granulovacuolar degeneration bodies (GVBs). CONCLUSIONS: These results support the notion that golgin A4 could serve as a diagnostic marker in Alzheimer disease. For validation of this notion, prospective multicenter diagnostic studies will evaluate golgin A4 as diagnostic marker for Alzheimer disease. Furthermore, it has to be determined whether the association of golgin A4 with GVBs is an epiphenomenon or whether golgin A4 plays a more direct role in Alzheimer disease, allowing it to serve as a target in therapeutic treatment strategies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that elevated CSF golgin A4 levels identify patients with Alzheimer disease.
Keywords:Alzheimer Disease, Biomarkers, Brain, Golgi Matrix Proteins, Vacuoles, Animals, Mice
Source:Neurology
ISSN:0028-3878
Publisher:American Academy of Neurology (U.S.A.)
Volume:91
Number:19
Page Range:e1799-e1808
Date:6 November 2018
Official Publication:https://doi.org/10.1212/WNL.0000000000006457
PubMed:View item in PubMed

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