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

• Published in: Neurology Vol. 93; no. 17; p. e1647
• Main Authors: Schindler, Suzanne E, Bollinger, James G, Ovod, Vitaliy, Mawuenyega, Kwasi G, Li, Yan, Gordon, Brian A, Holtzman, David M, Morris, John C, Benzinger, Tammie L S, Xiong, Chengjie, Fagan, Anne M, Bateman, Randall J
• Format: Journal Article
• Language: English
• Published: United States 22.10.2019
• Subjects: Age Factors; Aged; Amyloid beta-Peptides - blood; Amyloid beta-Peptides - cerebrospinal fluid; Amyloidosis - blood; Amyloidosis - diagnostic imaging; Amyloidosis - genetics; Apolipoprotein E4 - genetics; Biomarkers - blood; Brain - diagnostic imaging; Brain - metabolism; Female; Humans; Longitudinal Studies; Male; Middle Aged; Peptide Fragments - blood; Peptide Fragments - cerebrospinal fluid; Positron-Emission Tomography; Prognosis; tau Proteins - cerebrospinal fluid
• ISSN: 1526-632X
• DOI: 10.1212/WNL.0000000000008081

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. 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. 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 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 ( = 0.01). Plasma Aβ42/Aβ40, especially when combined with age and 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. This study provides Class II evidence that plasma Aβ42/Aβ40 levels accurately determine amyloid PET status in cognitively normal research participants.