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

Eline A.J. Willemse, Anne Sieben, Charisse Somers, Yannick Vermeiren, Naomi De Roeck, Maarten Timmers, Christine Van Broeckhoven, Bart De Vil, Patrick Cras, Peter P. De Deyn, Jean Jacques Martin, Charlotte E. Teunissen, Sebastiaan Engelborghs, Maria Bjerke*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)99-109
Number of pages11
JournalNeurobiology of aging
Volume108
DOIs
Publication statusPublished - Dec 2021
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Biomarker
  • Cerebrospinal fluid
  • Neurodegeneration
  • Neurogranin
  • Post-mortem

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