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Related Experiment Video

Updated: Aug 8, 2025

Absolute Quantification of Aβ1-42 in CSF Using a Mass Spectrometric Reference Measurement Procedure
08:40

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Predicting continuous amyloid PET values with CSF and plasma Aβ42/Aβ40.

Julie K Wisch1, Brian A Gordon2,3,4, Anna H Boerwinkle1

  • 1Department of Neurology Washington University in Saint Louis St. Louis Missouri USA.

Alzheimer'S & Dementia (Amsterdam, Netherlands)
|March 6, 2023
PubMed
Summary

Cerebrospinal fluid amyloid beta 42/40 ratio predicts continuous amyloid PET values across a wider range than plasma. This biomarker may aid in staging Alzheimer's disease.

Keywords:
CSF Aβ42/Aβ40PETbiomarker concordancemachine learningplasma Aβ42/Aβ40

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Area of Science:

  • Neuroscience
  • Biomarker Discovery
  • Alzheimer's Disease Research

Background:

  • Continuous measures of amyloid burden via positron emission tomography (PET) are increasingly used for Alzheimer's disease (AD) staging.
  • Amyloid beta (Aβ) levels in cerebrospinal fluid (CSF) and plasma are potential biomarkers for AD.

Purpose of the Study:

  • To evaluate if CSF and plasma Aβ42/Aβ40 ratios can predict continuous amyloid PET burden.
  • To determine the range of amyloid accumulation predictable by these fluid biomarkers.

Main Methods:

  • CSF and plasma Aβ42 and Aβ40 were measured using automated immunoassays and immunoprecipitation-mass spectrometry, respectively.
  • Amyloid PET imaging was performed using Pittsburgh Compound B (PiB).
  • Statistical models were used to assess the continuous relationship between fluid Aβ ratios and amyloid PET burden.

Main Results:

  • CSF Aβ42/Aβ40 predicted amyloid PET burden up to a high level of amyloid accumulation (69.8 Centiloids).
  • Plasma Aβ42/Aβ40 predicted amyloid PET burden only up to a lower level (33.4 Centiloids).
  • Most participants (87%) were cognitively normal, with a mean age of 69.0 years.

Conclusions:

  • CSF Aβ42/Aβ40 is a more comprehensive predictor of continuous amyloid plaque burden than plasma Aβ42/Aβ40.
  • CSF Aβ42/Aβ40 may serve as a valuable tool for staging Alzheimer's disease.
  • Plasma Aβ42/Aβ40 functions more as a dichotomous indicator of brain amyloidosis.