Cerebrospinal fluid tau, neurogranin, and neurofilament light in Alzheimer's disease

Cerebrospinal fluid (CSF) tau (total tau, T-tau), neurofilament light (NFL), and neurogranin (Ng) are potential biomarkers for neurode-generation in Alzheimer's disease (AD). It is unknown whether these biomarkers provide similar or complementary information in AD. We examined 93 patients with AD, 187 patients with mild cognitive impairment, and 109 controls. T-tau, Ng, and NFL were all predictors of AD diagnosis. Combinations improved the diagnostic accuracy (AUC 85.5% for T-tau, Ng, and NFL) compared to individual biomarkers (T-tau 80.8%; Ng 71.4%; NFL 77.7%). T-tau and Ng were highly correlated (rho = 0.79, P < 0.001) and strongly associated with beta-amyloid (A beta) pathology, and with longitudinal deterioration in cognition and brain structure, primarily in people with A beta pathology. NFL on the other hand was not associated with A beta pathology and was associated with cognitive decline and brain atrophy independent of A beta. T-tau, Ng, and NFL provide partly independent information about neuronal injury and may be combined to improve the diagnostic accuracy for AD. T-tau and Ng reflect A beta-dependent neurodegeneration, while NFL reflects neurodegeneration independently of A beta pathology.