TY - JOUR
T1 - Neurogranin as cerebrospinal fluid biomarker for Alzheimer disease
T2 - An assay comparison study
AU - Willemse, Eline A.J.
AU - De Vos, Ann
AU - Herries, Elizabeth M.
AU - Andreasson, Ulf
AU - Engelborghs, Sebastiaan
AU - Van Der Flier, Wiesje M.
AU - Scheltens, Philip
AU - Crimmins, Dan
AU - Ladenson, Jack H.
AU - Vanmechelen, Eugeen
AU - Zetterberg, Henrik
AU - Fagan, Anne M.
AU - Blennow, Kaj
AU - Bjerke, Maria
AU - Teunissen, Charlotte E.
N1 - Funding Information:
Employment or Leadership: E. Vanmechelen, ADx NeuroSciences. Consultant or Advisory Role: None declared. Stock Ownership: A. De Vos, ADx NeuroSciences; E. Vanmechelen, ADx NeuroSciences. Honoraria: None declared. Research Funding: E.A.J. Willemse, BIODEM laboratory, Institute Born-Bunge, University of Antwerp; A. De Vos, institutional funding from Agency for Innovation by Science and Technology. ZonMW. This study was part of the BIOMARKAPD project in the JPND programme (www.jpnd.eu) and financially supported by EMIF-AD, and the Agency for Innovation by Science and Technology (IWT O&O 140105). The work performed at the Institute Born-Bunge in Antwerp (Silver stain and Western blot experiments) was financially supported by a travel grant from Alzheimer Nederland. The brain banks of VU University Medical Center Amsterdam (The Netherlands) and the Institute Born-Bunge, University of Antwerp (Belgium) donated the brain homogenate sample. Expert Testimony: None declared. Patents: J. Ladenson, biomarkers of brain injury (Patent 7,985,555), Alzheimer’s diagnosis (Patent 8,481,277).
Funding Information:
Research Funding: E.A.J. Willemse, BIODEM laboratory, Institute Born-Bunge, University of Antwerp; A. De Vos, institutional funding from Agency for Innovation by Science and Technology. ZonMW. This study was part of the BIOMARKAPD project in the JPND pro-gramme (www.jpnd.eu) and financially supported by EMIF-AD, and the Agency for Innovation by Science and Technology (IWT O&O 140105). The work performed at the Institute Born-Bunge in Antwerp (Silver stain and Western blot experiments) was financially supported by a travel grant from Alzheimer Nederland. The brain banks of VU University Medical Center Amsterdam (The Netherlands) and the Institute Born-Bunge, University of Antwerp (Belgium) donated the brain homogenate sample.
Publisher Copyright:
© 2018 American Association for Clinical Chemistry.
PY - 2018/6
Y1 - 2018/6
N2 - BACKGROUND: Neurogranin in cerebrospinal fluid (CSF) correlates with cognitive decline and is a potential novel biomarker for Alzheimer disease (AD) dementia. We investigated the analytical and diagnostic performance of 3 commonly used neurogranin assays in the same cohort of patients to improve the interpretability of CSF neurogranin test results. METHODS: The neurogranin Erenna® assay from Washington University, St. Louis, MO (WashU); ELISA from ADx Neurosciences; and ELISA from Gothenburg University, Mölndal, Sweden (UGot), were compared using silver staining and Western blot after gel electrophoresis. Clinical performance of the 3 assays was compared in samples from individuals diagnosed with subjective cognitive decline (n 22), and in patients with AD (n 22), frontotemporal dementia (n 22), dementia with Lewy bodies (n 22), or vascular dementia (n 20), adjusted for sex and age. RESULTS: The assays detected different epitopes of neurogranin: the WashU assay detected the N-terminal part of neurogranin (S10-D23) and a C-terminal part (G49-G60), the ADx assay detected C-terminal neurogranin truncated at P75, and the UGot assay detected the C-terminal neurogranin with intact ending (D78). Spearman was 0.95 between ADx and WashU, 0.87 between UGot and WashU, and 0.81 between UGot and ADx. ANCOVA (analysis of covariance) showed group differences for ranked neurogranin concentrations in each assay (all P 0.05), with specific increases in AD. CONCLUSIONS: Although the 3 assays target different epitopes on neurogranin and have different calibrators, the high correlations and the similar group differences suggest that the different forms of neurogranin in CSF carry similar diagnostic information, at least in the context of neurodegenerative diseases.
AB - BACKGROUND: Neurogranin in cerebrospinal fluid (CSF) correlates with cognitive decline and is a potential novel biomarker for Alzheimer disease (AD) dementia. We investigated the analytical and diagnostic performance of 3 commonly used neurogranin assays in the same cohort of patients to improve the interpretability of CSF neurogranin test results. METHODS: The neurogranin Erenna® assay from Washington University, St. Louis, MO (WashU); ELISA from ADx Neurosciences; and ELISA from Gothenburg University, Mölndal, Sweden (UGot), were compared using silver staining and Western blot after gel electrophoresis. Clinical performance of the 3 assays was compared in samples from individuals diagnosed with subjective cognitive decline (n 22), and in patients with AD (n 22), frontotemporal dementia (n 22), dementia with Lewy bodies (n 22), or vascular dementia (n 20), adjusted for sex and age. RESULTS: The assays detected different epitopes of neurogranin: the WashU assay detected the N-terminal part of neurogranin (S10-D23) and a C-terminal part (G49-G60), the ADx assay detected C-terminal neurogranin truncated at P75, and the UGot assay detected the C-terminal neurogranin with intact ending (D78). Spearman was 0.95 between ADx and WashU, 0.87 between UGot and WashU, and 0.81 between UGot and ADx. ANCOVA (analysis of covariance) showed group differences for ranked neurogranin concentrations in each assay (all P 0.05), with specific increases in AD. CONCLUSIONS: Although the 3 assays target different epitopes on neurogranin and have different calibrators, the high correlations and the similar group differences suggest that the different forms of neurogranin in CSF carry similar diagnostic information, at least in the context of neurodegenerative diseases.
UR - http://www.scopus.com/inward/record.url?scp=85047958635&partnerID=8YFLogxK
U2 - 10.1373/clinchem.2017.283028
DO - 10.1373/clinchem.2017.283028
M3 - Article
C2 - 29523639
AN - SCOPUS:85047958635
SN - 0009-9147
VL - 64
SP - 927
EP - 937
JO - Clinical chemistry
JF - Clinical chemistry
IS - 6
ER -