Combination of CSF N-acetylaspartate and neurofilaments in multiple sclerosis

Neurology. 2009 Apr 14;72(15):1322-9. doi: 10.1212/WNL.0b013e3181a0fe3f.


Objective: Axonal degeneration is the likely cause of disease progression in multiple sclerosis (MS). Our previous results indicated that neuron-specific N-acetylaspartate (NAA) is a candidate CSF biomarker for disease progression in MS. The aim of this study was to explore the potential of NAA as an early biomarker of axonal damage in MS. Next, we wanted to know the additional value of measurement of NAA compared to other candidate markers for axonal damage, such as neurofilament subunits and tau protein.

Methods: Levels of NAA, neurofilament light, neurofilament heavy, and tau were determined in CSF of patients with clinically isolated syndrome (CIS, n = 38), relapsing-remitting MS (RRMS, n = 42), secondary progressive MS (SPMS, n = 28), and primary progressive MS (PPMS, n = 6); patients without neurologic disease (ND, n = 28); noninflammatory neurologic controls (n = 18); and inflammatory neurologic controls (n = 39).

Results: CSF NAA levels were decreased in patients with SPMS compared to ND controls, patients with CIS, and patients with RRMS. CSF NAA levels in patients with CIS and RRMS were similar to those in ND subjects. All axonal damage proteins showed specific patterns of changes and relations with disease activity measures. The neurofilament light chain levels were already increased in patients with CIS, especially in patients who converted to MS. The neurofilament heavy chain levels were highest in the patients with SPMS. Tau levels were similar in MS and ND.

Conclusions: CSF N-acetylaspartate (NAA) levels were not different from patients without neurologic disease in early stages of multiple sclerosis, though decreased as the disease progressed. Combining CSF NAA and neurofilament levels yields information on different phases of axonal pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / cerebrospinal fluid
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / cerebrospinal fluid
  • Axons / pathology
  • Biomarkers
  • Cohort Studies
  • Disease Progression
  • Humans
  • Magnetic Resonance Imaging
  • Multiple Sclerosis / cerebrospinal fluid*
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis, Chronic Progressive / cerebrospinal fluid
  • Multiple Sclerosis, Chronic Progressive / pathology
  • Multiple Sclerosis, Relapsing-Remitting / cerebrospinal fluid
  • Multiple Sclerosis, Relapsing-Remitting / pathology
  • Nerve Degeneration / pathology
  • Neurofilament Proteins / cerebrospinal fluid*
  • tau Proteins / cerebrospinal fluid


  • Amino Acids
  • Biomarkers
  • Neurofilament Proteins
  • tau Proteins
  • Aspartic Acid
  • N-acetylaspartate