Journal
NEUROLOGY
Volume 93, Issue 17, Pages E1647-E1659Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000008081
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Funding
- Alzheimer's Association Zenith
- Anonymous Foundation
- National Institute on Aging [NIH R56AG061900, P01AG026276, P01AG03991, P50AG05681]
- Barnes Jewish Hospital Foundation
- NIH [P30NS098577, R01EB009352, UL1TR000448]
- Eli Lilly/Avid Radiopharmaceuticals
- Barnes Jewish Hospital Foundation Willman Scholar Fund
- [K23AG053426]
- [K01AG053474]
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Objective We examined whether plasma beta-amyloid (A beta)42/A beta 40, as measured by a high-precision assay, accurately diagnosed brain amyloidosis using amyloid PET or CSF p-tau181/A beta 42 as reference standards. Methods Using an immunoprecipitation and liquid chromatography-mass spectrometry assay, we measured A beta 42/A beta 40 in plasma and CSF samples from 158 mostly cognitively normal individuals that were collected within 18 months of an amyloid PET scan. Results Plasma A beta 42/A beta 40 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/A beta 42 (AUC 0.85, 95% CI 0.79-0.92). The combination of plasma A beta 42/A beta 40, age, and APOE epsilon 4 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 A beta 42/A beta 40 (<0.1218) had a 15-fold greater risk of conversion to amyloid PET-positive compared to individuals with a negative plasma A beta 42/A beta 40 (p = 0.01). Conclusions Plasma A beta 42/A beta 40, especially when combined with age and APOE epsilon 4 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 A beta 42/A beta 40 are at increased risk for converting to amyloid PET-positive. Plasma A beta 42/A beta 40 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 A beta 42/A beta 40 levels accurately determine amyloid PET status in cognitively normal research participants.
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