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Abstract
Objective We examined whether plasma β-amyloid (Aβ)42/Aβ40, as measured by a high-precision assay, accurately diagnosed brain amyloidosis using amyloid PET or CSF p-tau181/Aβ42 as reference standards.
Methods Using an immunoprecipitation and liquid chromatography–mass spectrometry assay, we measured Aβ42/Aβ40 in plasma and CSF samples from 158 mostly cognitively normal individuals that were collected within 18 months of an amyloid PET scan.
Results Plasma Aβ42/Aβ40 had a high correspondence with amyloid PET status (receiver operating characteristic area under the curve [AUC] 0.88, 95% confidence interval [CI] 0.82–0.93) and CSF p-tau181/Aβ42 (AUC 0.85, 95% CI 0.79–0.92). The combination of plasma Aβ42/Aβ40, age, and APOE ε4 status had a very high correspondence with amyloid PET (AUC 0.94, 95% CI 0.90–0.97). Individuals with a negative amyloid PET scan at baseline and a positive plasma Aβ42/Aβ40 (<0.1218) had a 15-fold greater risk of conversion to amyloid PET-positive compared to individuals with a negative plasma Aβ42/Aβ40 (p = 0.01).
Conclusions Plasma Aβ42/Aβ40, especially when combined with age and APOE ε4 status, accurately diagnoses brain amyloidosis and can be used to screen cognitively normal individuals for brain amyloidosis. Individuals with a negative amyloid PET scan and positive plasma Aβ42/Aβ40 are at increased risk for converting to amyloid PET-positive. Plasma Aβ42/Aβ40 could be used in prevention trials to screen for individuals likely to be amyloid PET-positive and at risk for Alzheimer disease dementia.
Classification of evidence This study provides Class II evidence that plasma Aβ42/Aβ40 levels accurately determine amyloid PET status in cognitively normal research participants.
Glossary
- A4 Prevention Study=
- Anti-Amyloid Treatment in Alzheimer's Prevention Study;
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ANOVA=
- analysis of variance;
- AUC=
- area under the curve;
- CDR=
- Clinical Dementia Rating;
- CI=
- confidence interval;
- CV=
- coefficient of variation;
- DMSO=
- dimethyl sulfoxide;
- IPMS=
- immunoprecipitation mass spectrometry;
- NPA=
- negative percent agreement;
- p-tau=
- phosphorylated tau181;
- PiB=
- Pittsburgh compound B;
- PPA=
- positive percent agreement;
- QC=
- quality control;
- ROC=
- receiver operating characteristic;
- SUVR=
- standardized uptake value ratio
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 737
Class of Evidence: NPub.org/coe
Podcast: NPub.org/6dc9ia
- Received January 16, 2019.
- Accepted in final form June 17, 2019.
- © 2019 American Academy of Neurology
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