Amyloid-β--associated clinical decline occurs only in the presence of elevated P-tau

Arch Neurol. 2012 Jun;69(6):709-13. doi: 10.1001/archneurol.2011.3354.


Objective: To elucidate the relationship between the 2 hallmark proteins of Alzheimer disease (AD), amyloid-(Aβ) and tau, and clinical decline over time among cognitively normal older individuals.

Design: A longitudinal cohort of clinically and cognitively normal older individuals assessed with baseline lumbar puncture and longitudinal clinical assessments.

Setting: Research centers across the United States and Canada.

Patients: We examined 107 participants with a Clinical Dementia Rating (CDR) of 0 at baseline examination.

Main outcome measures: Using linear mixed effects models, we investigated the relationship between cerebrospinal fluid (CSF) phospho-tau 181 (p-tau(181p)),CSF Aβ(1-42), and clinical decline as assessed using longitudinal change in global CDR, CDR-Sum of Boxes, and the Alzheimer Disease Assessment Scale-cognitive subscale.

Results: We found a significant relationship between decreased CSF Aβ(1-42) and longitudinal change in global CDR,CDR-Sum of Boxes, and Alzheimer Disease Assessment Scale-cognitive subscale in individuals with elevated CSFp-tau(181p). In the absence of CSF p-tau(181p), the effect of CSF Aβ(1-42) on longitudinal clinical decline was not significantly different from 0.

Conclusions: In cognitively normal older individuals,A-associated clinical decline during a mean of 3 years may occur only in the presence of ongoing downstream neurodegeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Canada / epidemiology
  • Cohort Studies
  • Disease Progression
  • Female
  • Humans
  • Linear Models
  • Male
  • Peptide Fragments / cerebrospinal fluid*
  • Psychiatric Status Rating Scales
  • United States / epidemiology
  • tau Proteins / cerebrospinal fluid*


  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins