Cerebrospinal fluid neurogranin and YKL‐40 as biomarkers of Alzheimer's disease. Issue 1 (20th November 2015) - Janelidze, Shorena
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 (A β 42 and A β 40) 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 A β 40 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; A β 42/neurogranin, AUC = 0.849; A β 42/YKL‐40, AUC = 0.785), but the diagnostic accuracy was not better compared to CSF A β and tau (A β 42, AUC = 0.755; tau AUC = 0.858; A β 42/tau, AUC = 0.895; A β 42/A β 40, 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.