CSF neurofilaments in frontotemporal dementia compared with early onset Alzheimer's disease and controls

Dement Geriatr Cogn Disord. 2007;23(4):225-30. doi: 10.1159/000099473. Epub 2007 Feb 9.

Abstract

Background: Frontotemporal dementia (FTD) is pathologically heterogeneous, sometimes revealing intraneuronal inclusions of neurofilaments. We therefore measured CSF neurofilament profiles in patients with FTD, patients with early onset Alzheimer's disease (EAD) and healthy control subjects to explore the discriminative potential of CSF neurofilaments compared with the existing CSF biomarkers amyloid-beta(1-42), tau and tau phosphorylated at threonine-181.

Methods: CSF levels of light chain, heavy chain and hyperphosphorylated heavy chain neurofilaments (NfL, t-NfH and P-NfH) were compared between 17 subjects with FTD, 20 with EAD and 25 cognitively healthy controls.

Results: A subgroup of FTD patients had remarkably high CSF levels of both NfL and NfH. The degree of NfH phosphorylation was increased in FTD compared to both other groups. The levels of CSF NfL were significantly higher in EAD compared to controls.

Conclusion: Differences in CSF biomarker profiles might reflect differential involvement of neurofilaments and tau in FTD and EAD. The subgroup of FTD patients with high CSF neurofilament levels may have a different neuropathological substrate and future studies addressing this specific issue are needed.

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Amyloid beta-Peptides / metabolism
  • Biomarkers / cerebrospinal fluid
  • Biomarkers / metabolism
  • Dementia / cerebrospinal fluid*
  • Dementia / pathology
  • Female
  • Humans
  • Male
  • Matched-Pair Analysis
  • Middle Aged
  • Neurofilament Proteins / cerebrospinal fluid*
  • Neurofilament Proteins / metabolism
  • Peptide Fragments / cerebrospinal fluid
  • Peptide Fragments / metabolism
  • Phosphorylation
  • Reference Values
  • tau Proteins / cerebrospinal fluid*
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Neurofilament Proteins
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • neurofilament protein L
  • tau Proteins