Plasma Aβ42/40 ratio alone or combined with FDG-PET can accurately predict amyloid-PET positivity: a cross-sectional analysis from the AB255 Study

Alzheimers Res Ther. 2019 Dec 1;11(1):96. doi: 10.1186/s13195-019-0549-1.


Background: To facilitate population screening and clinical trials of disease-modifying therapies for Alzheimer's disease, supportive biomarker information is necessary. This study was aimed to investigate the association of plasma amyloid-beta (Aβ) levels with the presence of pathological accumulation of Aβ in the brain measured by amyloid-PET. Both plasma Aβ42/40 ratio alone or combined with an FDG-PET-based biomarker of neurodegeneration were assessed as potential AD biomarkers.

Methods: We included 39 cognitively normal subjects and 20 patients with mild cognitive impairment from the AB255 Study who had undergone PiB-PET scans. Total Aβ40 and Aβ42 levels in plasma (TP42/40) were quantified using ABtest kits. Subjects were dichotomized as Aβ-PET positive or negative, and the ability of TP42/40 to detect Aβ-PET positivity was assessed by logistic regression and receiver operating characteristic analyses. Combination of plasma Aβ biomarkers and FDG-PET was further assessed as an improvement for brain amyloidosis detection and diagnosis classification.

Results: Eighteen (30.5%) subjects were Aβ-PET positive. TP42/40 ratio alone identified Aβ-PET status with an area under the curve (AUC) of 0.881 (95% confidence interval [CI] = 0.779-0.982). Discriminating performance of TP42/40 to detect Aβ-PET-positive subjects yielded sensitivity and specificity values at Youden's cutoff of 77.8% and 87.5%, respectively, with a positive predictive value of 0.732 and negative predictive value of 0.900. All these parameters improved after adjusting the model for significant covariates. Applying TP42/40 as the first screening tool in a sequential diagnostic work-up would reduce the number of Aβ-PET scans by 64%. Combination of both FDG-PET scores and plasma Aβ biomarkers was found to be the most accurate Aβ-PET predictor, with an AUC of 0.965 (95% CI = 0.913-0.100).

Conclusions: Plasma TP42/40 ratio showed a relevant and significant potential as a screening tool to identify brain Aβ positivity in preclinical and prodromal stages of Alzheimer's disease.

Keywords: Amyloid-PET; Amyloid-beta; Biomarker; FDG-PET; Mild cognitive impairment; Plasma; Preclinical Alzheimer’s disease.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / metabolism
  • Amyloid / metabolism*
  • Amyloid beta-Peptides / blood
  • Amyloid beta-Peptides / metabolism*
  • Cognitive Dysfunction / diagnosis*
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / metabolism
  • Cross-Sectional Studies
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Longitudinal Studies
  • Male
  • Peptide Fragments / blood
  • Peptide Fragments / metabolism*
  • Positron-Emission Tomography


  • Amyloid
  • Amyloid beta-Peptides
  • Peptide Fragments
  • Fluorodeoxyglucose F18