Performance of aβ1-40, aβ1-42, total tau, and phosphorylated tau as predictors of dementia in a cohort of patients with mild cognitive impairment

J Alzheimers Dis. 2012;29(1):229-38. doi: 10.3233/JAD-2011-111349.


Mild cognitive impairment (MCI) is a common condition in the elderly which may remain stable along time (MCI-MCI) or evolve into Alzheimer's disease (MCI-AD) or other dementias. Cerebrospinal fluid (CSF) classical biomarkers, i.e., amyloid-β 1-42 (Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau) reflect the neuropathological changes taking place in AD brains, thus disclosing the disease in its prodromal phase. With the aim to evaluate the power of each biomarker and/or their combination in predicting AD progression, we have measured CSF Aβ1-40, Aβ1-42, t-tau, and p-tau in patients with AD, MCI-MCI, MCI-AD, and other neurological diseases without dementia (OND) followed up for four years. Aβ1-42 levels were significantly lower in AD and MCI-AD than in MCI-MCI. T-tau and p-tau levels were significantly increased in AD and MCI-AD versus OND and MCI-MCI. The Aβ1-42/Aβ1-40 ratio showed a significant decrease in AD and MCI-AD as compared to MCI-MCI. Both Aβ1-42/t-tau and Aβ1-42/p-tau ratios showed significantly decreased values in AD and MCI-AD with respect to OND and MCI-MCI. Aβ1-42/p-tau ratio was the best parameter for discriminating MCI-AD from MCI-MCI (sensitivity 81%, specificity 95%), being also correlated with the annual change rate in the Mini Mental State Examination annual change rate score (MMSE-ACR, rS = -0.71, p < 0.0001). Survival analysis showed that 81% of MCI with a low Aβ1-42/p-tau ratio (<1372) progressed to AD. The best model of logistic regression analysis retained Aβ1-42 and p-tau (sensitivity 75%, 95%CI: 70-80%; specificity 96%, 95%CI: 94-98%). We can conclude that Aβ1-42 and p-tau reliably predict conversion to AD in MCI patients.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Cognitive Dysfunction / cerebrospinal fluid*
  • Cognitive Dysfunction / diagnosis*
  • Cohort Studies
  • Dementia / cerebrospinal fluid*
  • Dementia / diagnosis*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid*
  • Phosphorylation
  • Predictive Value of Tests
  • tau Proteins / cerebrospinal fluid*


  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • tau Proteins