Neurogranin as biomarker in CSF is non-specific to Alzheimer's disease dementia

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 neu-ropathological 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 co-hort 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 with-out added value for AD differential diagnosis. (C) 2021 The Authors. Published by Elsevier Inc.

Automated summary

The study found that CSF Ng concentrations differ among AD, non-AD, and control groups, but are not associated with tissue Ng concentrations. CSF Ng is a general biomarker for synaptic degeneration, strongly correlated with CSF tau, but without added value for the differential diagnosis of AD.