Association between cerebrospinal fluid and plasma neurodegeneration biomarkers with brain atrophy in Alzheimer's disease

Neurobiol Aging. 2017 Oct:58:14-29. doi: 10.1016/j.neurobiolaging.2017.06.002. Epub 2017 Jun 17.


The aggregation and deposition of amyloid-β (Aβ) peptides into plaques is an early event in Alzheimer's disease (AD), which is followed by different aspects of neurodegeneration that can be measured in the cerebrospinal fluid (CSF) or plasma using neurofilament light (NFL), neurogranin (Ng), total Tau (T-Tau), and phosphorylated tau (P-Tau) levels. The relationship between these biomarkers and regional brain atrophy across the different stages of AD remains largely unexplored. In this study, we assessed whether NFL, Ng, T-Tau, and P-Tau levels in CSF and NFL in plasma are associated with cortical thinning and subcortical volume loss in cognitively normal, mild cognitive impairment, and AD subjects with and without Aβ pathology. Our main findings showed that CSF NFL levels were associated with brain atrophy in all groups, but plasma NFL only correlated with atrophy in symptomatic cases. In contrast, Ng was associated with regional brain atrophy only in individuals with Aβ pathology. Altogether, our main findings suggest that Ng is strongly associated with Aβ pathology, whereas NFL is more unspecific.

Keywords: Cortical thickness; Neurofilament light; Neurogranin; Subcortical volumes; Tau.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism
  • Atrophy
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Brain / pathology*
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nerve Degeneration*
  • Neurofilament Proteins / blood*
  • Neurofilament Proteins / cerebrospinal fluid*
  • Neurogranin / cerebrospinal fluid*
  • Organ Size
  • Plaque, Amyloid / metabolism
  • tau Proteins / cerebrospinal fluid*


  • Amyloid beta-Peptides
  • Biomarkers
  • Neurofilament Proteins
  • neurofilament protein L
  • tau Proteins
  • Neurogranin