CSF Phosphorylated Tau Protein Correlates With Neocortical Neurofibrillary Pathology in Alzheimer's Disease

Brain. 2006 Nov;129(Pt 11):3035-41. doi: 10.1093/brain/awl269. Epub 2006 Sep 29.

Abstract

Hyperphosphorylated tau protein (P-tau) in CSF is a core biomarker candidate of Alzheimer's disease. Hyperphosphorylation of tau is thought to lead to neurofibrillary changes, a neuropathological hallmark of this type of dementia. Currently, the question is unresolved whether CSF levels of P-tau reflect neurofibrillary changes within the brain of a patient with the illness. Twenty-six patients were included with intra-vitam CSF as well as post-mortem neuropathological data. In the CSF, P-tau phosphorylated at threonine 231 (P-tau231P) was analysed. Post-mortem, scores of neurofibrillary tangles (NFT) and neuritic plaques (NP) were assessed in frontal, temporal, parietal and hippocampal cortical areas. In the same cortical regions, load of hyperphosphorylated tau protein (HP-tau load) was determined. Concentrations of P-tau231P were measured in frontal cortex homogenates. We found significant correlations between CSF P-tau231P concentrations and scores of NFTs and HP-tau load in all neocortical regions studied. The score of NPs was correlated with CSF P-tau231P only within the frontal cortex. There was a correlation between P-tau231P in CSF and brain homogenates. These findings indicate that CSF P-tau231P may serve as an in vivo surrogate biomarker of neurofibrillary pathology in Alzheimer's disease.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Biomarkers / cerebrospinal fluid
  • Female
  • Frontal Lobe / chemistry
  • Frontal Lobe / pathology
  • Hippocampus / pathology
  • Humans
  • Male
  • Neocortex / chemistry
  • Neocortex / pathology*
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology*
  • Parietal Lobe / pathology
  • Phosphorylation
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • Temporal Lobe / pathology
  • tau Proteins / analysis
  • tau Proteins / cerebrospinal fluid*

Substances

  • Biomarkers
  • tau Proteins