Plasma Aβ42/40 Ratio Detects Early Stages of Alzheimer's Disease and Correlates with CSF and Neuroimaging Biomarkers in the AB255 Study

J Prev Alzheimers Dis. 2019;6(1):34-41. doi: 10.14283/jpad.2018.41.


Background: Easily accessible biomarkers are needed for the early identification of individuals at risk of developing Alzheimer's disease (AD) in large population screening strategies.

Objectives: This study evaluated the potential of plasma β-amyloid (Aβ) biomarkers in identifying early stages of AD and predicting cognitive decline over the following two years.

Design: Total plasma Aβ42/40 ratio (TP42/40) was determined in 83 cognitively normal individuals (CN) and 145 subjects with amnestic mild cognitive impairment (a-MCI) stratified by an FDG-PET AD-risk pattern.

Results: Significant lower TP42/40 ratio was found in a-MCI patients compared to CN. Moreover, a-MCIs with a high-risk FDG-PET pattern for AD showed even lower plasma ratio levels. Low TP42/40 at baseline increased the risk of progression to dementia by 70%. Furthermore, TP42/40 was inversely associated with neocortical amyloid deposition (measured with PiB-PET) and was concordant with the AD biomarker profile in cerebrospinal fluid (CSF).

Conclusions: TP42/40 demonstrated value in the identification of individuals suffering a-MCI, in the prediction of progression to dementia, and in the detection of underlying AD pathology revealed by FDG-PET, Amyloid-PET and CSF biomarkers, being, thus, consistently associated with all the well-established indicators of AD.

Keywords: Alzheimer’s disease; Aβ ratio; biomarker; plasma; β-amyloid (Aβ).

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / blood*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Aniline Compounds / metabolism
  • Apolipoproteins E / genetics
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cognitive Dysfunction / blood
  • Cross-Sectional Studies
  • Early Diagnosis*
  • Female
  • Fluorodeoxyglucose F18 / metabolism
  • Genotype
  • Humans
  • Male
  • Neuroimaging
  • Peptide Fragments / blood*
  • Peptide Fragments / cerebrospinal fluid
  • Phosphorylation
  • Plaque, Amyloid / metabolism
  • Positron-Emission Tomography
  • Prodromal Symptoms
  • Thiazoles / metabolism
  • tau Proteins / cerebrospinal fluid


  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Apolipoproteins E
  • Biomarkers
  • Peptide Fragments
  • Thiazoles
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Fluorodeoxyglucose F18