Plasma Aβ/Aβ is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum.

INTRODUCTION

The availability of amyloid beta (Aβ) targeting therapies for Alzheimer's disease (AD) is increasing the demand for scalable biomarkers that are sensitive to early cerebral Aβ accumulation.

METHODS

We evaluated fully-automated Lumipulse plasma Aβ/Aβ immunoassays for detecting cerebral Aβ in 457 clinically unimpaired (CU) and clinically impaired (CI) Stanford Alzheimer's Disease Research Center (Stanford ADRC) participants and 186 CU in the Stanford Aging and Memory Study (SAMS). Longitudinal change in ADRC plasma Aβ/Aβ and cognition and cross-sectional associations with SAMS memory and tau positron emission tomography (PET) were examined.

RESULTS

Plasma Aβ/Aβ exhibited high performance in detecting amyloid positivity defined by PET (area under the curve [AUC]: 0.885, 95% confidence interval [CI]: 0.816-0.955). Once abnomal, plasma Aβ/Aβ remained low and predicted cognitive decline in both CU and CI individuals. Among SAMS CU, plasma Aβ/Aβ was associated with poorer hippocampal-dependent memory and elevated tau accumulation.

DISCUSSION

Lumipulse plasma Aβ/Aβ is a scalable assay for detection of cerebral Aβ and prediction of risk for cognitive decline across the AD continuum.

HIGHLIGHTS

Lumipulse plasma amyloid beta (Aβ)/Aβ exhibited high accuracy in detecting amyloid positivity. Plasma amyloid-positive (Aβ+) individuals exhibited stability of Aβ/Aβ over time. Plasma Aβ/Aβ predicted future cognitive decline across the Alzheimer's disease (AD) spectrum. Plasma Aβ/Aβ was sensitive to memory and tau burden in clinically unimpaired older adults.