TY - JOUR
T1 - Neurogranin as biomarker in CSF is non-specific to Alzheimer's disease dementia
AU - Willemse, Eline A. J.
AU - Sieben, Anne
AU - Somers, Charisse
AU - Vermeiren, Yannick
AU - de Roeck, Naomi
AU - Timmers, Maarten
AU - van Broeckhoven, Christine
AU - de Vil, Bart
AU - Cras, Patrick
AU - de Deyn, Peter P.
AU - Martin, Jean-Jacques
AU - Teunissen, Charlotte E.
AU - Engelborghs, Sebastiaan
AU - Bjerke, Maria
N1 - Funding Information:
The authors thank Hanne Struyfs, Ellis Niemantsverdriet, Ellen De Roeck and Jill Luyckx for recruiting part of the control subjects. Additionally we thank Jill Luyckx for excellent technical assistance. This research was in part supported by the University Research Fund of the University of Antwerp, Institute Born-Bunge and an unrestricted research grant from Janssen Pharmaceutica. We thank Alzheimer Nederland for granting a travel fellowship (WE.15-2016-04) for financial support of this research. YV was a senior postdoctoral research fellow financed by VITO-FWO (Flemish Institute for Technological Research and Scientific Research Fund Flanders; #12Z1620N).
Publisher Copyright:
© 2021
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - We aimed to evaluate the specificity of neurogranin (Ng) for Alzheimer's disease (AD) in a dementia cohort. Cerebrospinal fluid (CSF) Ng was measured (ELISA) in two independent cohorts: (1) clinical (n = 116; age 72±11 years): AD, non-AD (+high T-tau), and controls; and (2) autopsy-confirmed (n = 97; age 71±11 years): AD and non-AD, and 50 controls (age 60±6 years). In 16 autopsy-confirmed AD and 8 control subjects, Ng was measured in tissue (BA6+BA22). Ng was compared across diagnostic groups or neuropathological staging using multilinear regression models. Median[IQR] Ng concentrations were elevated in AD (414[315–499]pg/mL) and non-AD (464[319–699]pg/mL) compared to controls (260[193–306]pg/mL), but highest in AD-high-T-tau (874[716, 1148] pg/mL) and Creutzfeldt-Jakob disease (CJD; 828[703–1373]pg/mL) in cohort 1 (p < 0.01), but not in cohort 2: AD: 358[249–470]pg/mL; non-AD:245[137–416]pg/mL; controls: 259[193–370]pg/mL. Ng and tau biomarkers strongly correlated (r = 0.4–0.9, p < 0.05), except in CJD. CSF Ng concentrations were not associated with neuropathological AD hallmarks, nor with tissue Ng concentrations. CSF Ng is a general biomarker for synaptic degeneration, strongly correlating with CSF tau, but without added value for AD differential diagnosis.
AB - We aimed to evaluate the specificity of neurogranin (Ng) for Alzheimer's disease (AD) in a dementia cohort. Cerebrospinal fluid (CSF) Ng was measured (ELISA) in two independent cohorts: (1) clinical (n = 116; age 72±11 years): AD, non-AD (+high T-tau), and controls; and (2) autopsy-confirmed (n = 97; age 71±11 years): AD and non-AD, and 50 controls (age 60±6 years). In 16 autopsy-confirmed AD and 8 control subjects, Ng was measured in tissue (BA6+BA22). Ng was compared across diagnostic groups or neuropathological staging using multilinear regression models. Median[IQR] Ng concentrations were elevated in AD (414[315–499]pg/mL) and non-AD (464[319–699]pg/mL) compared to controls (260[193–306]pg/mL), but highest in AD-high-T-tau (874[716, 1148] pg/mL) and Creutzfeldt-Jakob disease (CJD; 828[703–1373]pg/mL) in cohort 1 (p < 0.01), but not in cohort 2: AD: 358[249–470]pg/mL; non-AD:245[137–416]pg/mL; controls: 259[193–370]pg/mL. Ng and tau biomarkers strongly correlated (r = 0.4–0.9, p < 0.05), except in CJD. CSF Ng concentrations were not associated with neuropathological AD hallmarks, nor with tissue Ng concentrations. CSF Ng is a general biomarker for synaptic degeneration, strongly correlating with CSF tau, but without added value for AD differential diagnosis.
KW - Alzheimer's disease
KW - Biomarker
KW - Cerebrospinal fluid
KW - Neurodegeneration
KW - Neurogranin
KW - Post-mortem
UR - http://www.scopus.com/inward/record.url?scp=85115132939&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2021.08.002
DO - 10.1016/j.neurobiolaging.2021.08.002
M3 - Article
C2 - 34551375
SN - 0197-4580
VL - 108
SP - 99
EP - 109
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -