Cerebrospinal fluid neurogranin and YKL-40 as biomarkers of Alzheimer's disease

Shorena Janelidze; Joakim Hertze; Henrik Zetterberg; Maria Landqvist Waldö; Alexander Santillo; Kaj Blennow; Oskar Hansson

doi:10.1002/acn3.266

Cerebrospinal fluid neurogranin and YKL-40 as biomarkers of Alzheimer's disease

Ann Clin Transl Neurol. 2015 Nov 20;3(1):12-20. doi: 10.1002/acn3.266. eCollection 2016 Jan.

Authors

Shorena Janelidze¹, Joakim Hertze², Henrik Zetterberg³, Maria Landqvist Waldö⁴, Alexander Santillo², Kaj Blennow⁵, Oskar Hansson²

Affiliations

¹ Clinical Memory Research Unit Department of Clinical Sciences, Malmö Lund University Malmö Sweden.
² Clinical Memory Research Unit Department of Clinical Sciences, Malmö Lund University Malmö Sweden; Memory Clinic Skåne University Hospital Malmö Sweden.
³ Clinical Neurochemistry Laboratory Institute of Neuroscience and Physiology Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden; Department of Molecular Neuroscience UCL Institute of Neurology Queen Square London United Kingdom.
⁴ Memory Clinic Skåne University Hospital Malmö Sweden; Section of Geriatric Psychiatry Department of Clinical Sciences Lund University Lund Sweden.
⁵ Clinical Neurochemistry Laboratory Institute of Neuroscience and Physiology Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden.

Abstract

Objective: Widespread implementation of cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) in clinical settings requires improved accuracy for diagnosis of prodromal disease and for distinguishing AD from non-AD dementias. Novel and promising CSF biomarkers include neurogranin, a marker of synaptic degeneration, and YKL-40, a marker of neuroinflammation.

Methods: CSF neurogranin and YKL-40 were measured in a cohort of 338 individuals including cognitively healthy controls and patients with stable mild cognitive impairment (sMCI), MCI who later developed AD (MCI-AD), AD dementia, Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), vascular dementia (VaD), and frontotemporal dementia (FTD). The diagnostic accuracy of neurogranin and YKL-40 were compared with the core AD biomarkers, β-amyloid (Aβ42 and Aβ40) and tau.

Results: Neurogranin levels were increased in AD and decreased in non-AD dementia compared with healthy controls. As a result, AD patients showed considerably higher CSF levels of neurogranin than DLB/PDD, VaD and FTD patients. CSF YKL-40 levels were increased in AD compared with DLB/PDD but not with VaD or FTD. Neither CSF neurogranin nor YKL-40 levels differed significantly between sMCI patients and MCI-AD patients. Both biomarkers correlated positively with CSF Aβ40 and tau. CSF neurogranin and YKL-40 could separate AD dementia from non-AD dementias (neurogranin, area under the curve [AUC] = 0.761; YKL-40, AUC = 0.604; Aβ42/neurogranin, AUC = 0.849; Aβ42/YKL-40, AUC = 0.785), but the diagnostic accuracy was not better compared to CSF Aβ and tau (Aβ42, AUC = 0.755; tau AUC = 0.858; Aβ42/tau, AUC = 0.895; Aβ42/Aβ40, AUC = 0.881). Similar results were obtained when separating sMCI from MCI-AD cases.

Interpretation: CSF neurogranin and YKL-40 do not improve the diagnostic accuracy of either prodromal AD or AD dementia when compared to the core CSF AD biomarkers. Nevertheless, the CSF level of neurogranin is selectively increased in AD dementia, whereas YKL-40 is increased in both AD and FTD suggesting that synaptic degeneration and glial activation may be important in these neurodegenerative conditions.