Data from: High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis

Objective: We examined whether plasma Aβ42/Aβ40, as measured by a high
precision assay, accurately diagnosed brain amyloidosis using amyloid PET
or CSF pTau181/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 eighteen months of an
amyloid PET scan. Results: Plasma Aβ42/Aβ40 had a high correspondence with
amyloid PET status (ROC AUC 0.88, 95% confidence intervals [CI] 0.82-0.93)
and CSF pTau181/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 I evidence
that plasma Aβ42/Aβ40, as measured by a liquid chromatography-mass
spectrometry assay, accurately diagnoses brain amyloidosis in cognitively
normal research participants.