Cerebrospinal fluid levels of neurogranin and YKL-40 in mild cognitive impairment due to Alzheimer's disease or vascular dementia

J Alzheimers Dis. 2026 Jan 13:13872877251411336. doi: 10.1177/13872877251411336. Online ahead of print.

ABSTRACT

BackgroundMarkers of synaptic degeneration and neuroinflammation have been investigated in memory clinic cohorts, but less is known about their role in community-dwelling subjects.ObjectiveTo investigate baseline cerebrospinal fluid (CSF) levels of neurogranin and YKL-40 in community-dwelling subjects with mild cognitive impairment (MCI) who had not yet sought help for their cognitive decline.MethodsWe recruited and characterized 107 subjects, who at the clinical baseline examination were found to have MCI. Based on the clinical progression at a 3-year follow-up, the individuals were classified as MCI-Alzheimer's disease (MCI-AD, n = 40), MCI-vascular dementia (MCI-VaD, n = 25), and stable MCI (sMCI, n = 42).ResultsBaseline CSF neurogranin level was elevated in the MCI-AD group compared with the MCI-VaD and sMCI groups (p = 0.02 and p < 0.001, respectively), and baseline CSF YKL-40 level was higher in the MCI-AD group than in the sMCI group (p = 0.01). Neurogranin, and to a lesser extent YKL-40, correlated positively with CSF levels of total tau and phosphorylated tau₁₈₁ in all study groups. However, in receiver operator characteristics analyses, neurogranin and YKL-40 used alone or in combination had a moderate diagnostic accuracy that was lower than that of the core AD biomarkers (amyloid-β₄₂, total tau, and phosphorylated tau₁₈₁).ConclusionsThis study shows that neurogranin and YKL-40 in CSF are elevated in MCI-AD compared with sMCI, and neurogranin was also higher in MCI-AD than in MCI-VaD. Neurogranin and YKL-40 had a moderate diagnostic accuracy, but they could still be of value to characterize the clinical consequences of postsynaptic dysfunction and neuroinflammation.

PMID:41530948 | DOI:10.1177/13872877251411336