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

• Published in: Alzheimer's & dementia 2024-12
• Main Authors: Trelle, Alexandra N, Young, Christina B, Vossler, Hillary, Ramos Benitez, Javier, Cody, Karly A, Mendiola, Justin H, Swarovski, Michelle S, Guen, Yann Le, Feinstein, Igor, Butler, Robert R, Channappa, Divya, Romero, America, Park, Jennifer, Shahid-Besanti, Marian, Corso, Nicole K, Chau, Kelly, Smith, Amanda N, Skylar-Scott, Irina, Yutsis, Maya V, Fredericks, Carolyn A, Tian, Lu, Younes, Kyan, Kerchner, Geoffrey A, Deutsch, Gayle K, Davidzon, Guido A, Sha, Sharon J, Henderson, Victor W, Longo, Frank M, Greicius, Michael D, Wyss-Coray, Tony, Andreasson, Katrin I, Poston, Kathleen L, Wagner, Anthony D, Mormino, Elizabeth C, Wilson, Edward N
• Format: Article
• Language: English
• ISSN: 1552-5279; 1552-5279
• DOI: 10.1002/alz.14442

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.INTRODUCTIONThe 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.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.METHODSWe 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.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.RESULTSPlasma 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.Lumipulse plasma Aβ42/Aβ40 is a scalable assay for detection of cerebral Aβ and prediction of risk for cognitive decline across the AD continuum.DISCUSSIONLumipulse plasma Aβ42/Aβ40 is a scalable assay for detection of cerebral Aβ and prediction of risk for cognitive decline across the AD continuum.Lumipulse plasma amyloid beta (Aβ)42/Aβ40 exhibited high accuracy in detecting amyloid posit