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
PY - 2021/12
Y1 - 2021/12
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
U2 - 10.1016/j.neurobiolaging.2021.08.002
DO - 10.1016/j.neurobiolaging.2021.08.002
M3 - Article
AN - SCOPUS:85115132939
SN - 0197-4580
VL - 108
SP - 99
EP - 109
JO - Neurobiology of aging
JF - Neurobiology of aging
ER -