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

EMBO Mol Med. 2016 Oct 4;8(10):1184-1196. doi: 10.15252/emmm.201606540. Print 2016 Oct.


Cerebrospinal fluid (CSF) tau (total tau, T-tau), neurofilament light (NFL), and neurogranin (Ng) are potential biomarkers for neurodegeneration 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 (ρ = 0.79, P < 0.001) and strongly associated with β-amyloid (Aβ) pathology, and with longitudinal deterioration in cognition and brain structure, primarily in people with Aβ pathology. NFL on the other hand was not associated with Aβ pathology and was associated with cognitive decline and brain atrophy independent of Aβ. 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 Aβ-dependent neurodegeneration, while NFL reflects neurodegeneration independently of Aβ pathology.

Keywords: Alzheimer's; CSF; biomarker; neurodegeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / pathology*
  • Biomarkers / cerebrospinal fluid
  • Cerebrospinal Fluid / chemistry*
  • Humans
  • Longitudinal Studies
  • Neurofilament Proteins / analysis*
  • Neurogranin / analysis*
  • tau Proteins / analysis*


  • Biomarkers
  • MAPT protein, human
  • Neurofilament Proteins
  • neurofilament protein L
  • tau Proteins
  • Neurogranin