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Neurology. 2019 Aug 1. pii: 10.1212/WNL.0000000000008081. doi: 10.1212/WNL.0000000000008081. [Epub ahead of print]

High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis.

Author information

1
From the Department of Neurology (S.E.S., J.G.B., V.O., K.G.M., D.M.H., J.C.M., T.L.S.B., C.X., A.M.F., R.J.B.), Knight Alzheimer's Disease Research Center (S.E.S., B.A.G., D.M.H., J.C.M., T.L.S.B., C.X., A.M.F., R.J.B.), Division of Biostatistics (Y.L., C.X.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Hope Center for Neurological Disorders (D.M.H., A.M.F., R.J.B.), Washington University School of Medicine, St. Louis, MO.
2
From the Department of Neurology (S.E.S., J.G.B., V.O., K.G.M., D.M.H., J.C.M., T.L.S.B., C.X., A.M.F., R.J.B.), Knight Alzheimer's Disease Research Center (S.E.S., B.A.G., D.M.H., J.C.M., T.L.S.B., C.X., A.M.F., R.J.B.), Division of Biostatistics (Y.L., C.X.), Mallinckrodt Institute of Radiology (B.A.G., T.L.S.B.), and Hope Center for Neurological Disorders (D.M.H., A.M.F., R.J.B.), Washington University School of Medicine, St. Louis, MO. batemanr@wustl.edu.

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.

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