Staging of neurofibrillary pathology in Alzheimer's disease: a study of the BrainNet Europe Consortium

Brain Pathol. 2008 Oct;18(4):484-96. doi: 10.1111/j.1750-3639.2008.00147.x. Epub 2008 Mar 26.

Abstract

It has been recognized that molecular classifications will form the basis for neuropathological diagnostic work in the future. Consequently, in order to reach a diagnosis of Alzheimer's disease (AD), the presence of hyperphosphorylated tau (HP-tau) and beta-amyloid protein in brain tissue must be unequivocal. In addition, the stepwise progression of pathology needs to be assessed. This paper deals exclusively with the regional assessment of AD-related HP-tau pathology. The objective was to provide straightforward instructions to aid in the assessment of AD-related immunohistochemically (IHC) detected HP-tau pathology and to test the concordance of assessments made by 25 independent evaluators. The assessment of progression in 7-microm-thick sections was based on assessment of IHC labeled HP-tau immunoreactive neuropil threads (NTs). Our results indicate that good agreement can be reached when the lesions are substantial, i.e., the lesions have reached isocortical structures (stage V-VI absolute agreement 91%), whereas when only mild subtle lesions were present the agreement was poorer (I-II absolute agreement 50%). Thus, in a research setting when the extent of lesions is mild, it is strongly recommended that the assessment of lesions should be carried out by at least two independent observers.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging / pathology
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / physiopathology
  • Brain / metabolism
  • Brain / pathology*
  • Brain / physiopathology
  • Disease Progression
  • Female
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Middle Aged
  • Neocortex / metabolism
  • Neocortex / pathology
  • Neocortex / physiopathology
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology*
  • Neurons / metabolism
  • Neurons / pathology*
  • Observer Variation
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • Staining and Labeling / methods
  • tau Proteins / analysis
  • tau Proteins / metabolism*

Substances

  • tau Proteins