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Updated: Aug 8, 2025

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Absolute Quantification of Aβ1-42 in CSF Using a Mass Spectrometric Reference Measurement Procedure
Published on: March 21, 2017
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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
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.
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.

