Clinical validity of A beta-protein deposition staging in brain aging and Alzheimer disease

J Neuropathol Exp Neurol. 2001 Oct;60(10):946-52. doi: 10.1093/jnen/60.10.946.


Braak's neurofibrillary tangle (NFT) pathology staging system of Alzheimer disease (AD) correlates generally with clinical data. Recently, Braak's group proposed an Abeta-protein staging based on the progression of amyloid deposition in the medial temporal lobe. To examine its clinical validity and evaluate whether it adds predictive power to NFT-based staging, we performed a study comparing both neuropathological classifications with clinical dementia rating scale (CDR) scores in a large autopsy series. The 2 neuropathological staging systems were strongly correlated. Their association with clinical severity was highly significant. However, the strength of the relationship was greater for NFT-based staging. It accounted for 26.5% of the variability in clinical severity, Abeta-protein-based staging for 13.0%, and age for 4.4%. Compared to NFT-based staging, the Abeta-protein-based system was less able to distinguish mild cognitive changes from dementia and showed marked overlap among the various stages of cognitive decline. In a multivariate model, NFT and age together accounted for 27.2% of the clinical variability and the addition of Abeta-protein deposition staging could only explain an extra 2.9%. Our data support the close relationship between NFT progression and amyloid formation within the medial temporal lobe proposed by Braak's group but demonstrate the limited value of Abeta-protein deposition staging in terms of clinicopathological correlations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Validation Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / metabolism*
  • Aging / pathology*
  • Alzheimer Disease / classification
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides / analysis
  • Amyloid beta-Peptides / metabolism*
  • Brain / metabolism*
  • Brain / pathology*
  • Cognition Disorders / classification
  • Cognition Disorders / pathology
  • Cognition Disorders / psychology
  • Female
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology
  • Statistics, Nonparametric


  • Amyloid beta-Peptides