Plasma Aβ42/Aβ40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2024-12-23 DOI:10.1002/alz.14442

Alexandra N. Trelle, Christina B. Young, Hillary Vossler, Javier Ramos Benitez, Karly A. Cody, Justin H. Mendiola, Michelle S. Swarovski, Yann Le Guen, Igor Feinstein, Robert R. Butler III, Divya Channappa, America Romero, Jennifer Park, Marian Shahid-Besanti, Nicole K. Corso, Kelly Chau, Amanda N. Smith, Irina Skylar-Scott, Maya V. Yutsis, Carolyn A. Fredericks, Lu Tian, Kyan Younes, Geoffrey A. Kerchner, Gayle K. Deutsch, Guido A. Davidzon, Sharon J. Sha, Victor W. Henderson, Frank M. Longo, Michael D. Greicius, Tony Wyss-Coray, Katrin I. Andreasson, Kathleen L. Poston, Anthony D. Wagner, Elizabeth C. Mormino, Edward N. Wilson

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Abstract

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 Aβ₄₂/Aβ₄₀ 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 Aβ₄₂/Aβ₄₀ and cognition and cross-sectional associations with SAMS memory and tau positron emission tomography (PET) were examined.

RESULTS

Plasma Aβ₄₂/Aβ₄₀ 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 Aβ₄₂/Aβ₄₀ remained low and predicted cognitive decline in both CU and CI individuals. Among SAMS CU, plasma Aβ₄₂/Aβ₄₀ was associated with poorer hippocampal-dependent memory and elevated tau accumulation.

DISCUSSION

Lumipulse plasma Aβ₄₂/Aβ₄₀ 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)₄₂/Aβ₄₀ exhibited high accuracy in detecting amyloid positivity.
Plasma amyloid-positive (Aβ+) individuals exhibited stability of Aβ₄₂/Aβ₄₀ over time.
Plasma Aβ₄₂/Aβ₄₀ predicted future cognitive decline across the Alzheimer's disease (AD) spectrum.
Plasma Aβ₄₂/Aβ₄₀ was sensitive to memory and tau burden in clinically unimpaired older adults.

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血浆Aβ42/Aβ40对早期大脑淀粉样蛋白积累敏感，并预测阿尔茨海默病谱系中认知能力下降的风险

淀粉样蛋白（Aβ）靶向治疗阿尔茨海默病（AD）的可用性增加了对早期大脑Aβ积累敏感的可扩展生物标志物的需求。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.