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Plasma Aß42/Aß40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum.

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Plasma Aß42/Aß40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum. Alzheimer's & dementia : the journal of the Alzheimer's Association Trelle, A. N., Young, C. B., Vossler, H., Ramos Benitez, J., Cody, K. A., Mendiola, J. H., Swarovski, M. S., Guen, Y. L., Feinstein, I., Butler, R. R., Channappa, D., Romero, A., Park, J., Shahid-Besanti, M., Corso, N. K., Chau, K., Smith, A. N., Skylar-Scott, I., Yutsis, M. V., Fredericks, C. A., Tian, L., Younes, K., Kerchner, G. A., Deutsch, G. K., Davidzon, G. A., Sha, S. J., Henderson, V. W., Longo, F. M., Greicius, M. D., Wyss-Coray, T., Andreasson, K. I., Poston, K. L., Wagner, A. D., Mormino, E. C., Wilson, E. N. 2024

Abstract

The availability of amyloid beta (Aß) targeting therapies for Alzheimer's disease (AD) is increasing the demand for scalable biomarkers that are sensitive to early cerebral Aß accumulation.We evaluated fully-automated Lumipulse plasma Aß42/Aß40 immunoassays for detecting cerebral Aß 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 Aß42/Aß40 and cognition and cross-sectional associations with SAMS memory and tau positron emission tomography (PET) were examined.Plasma Aß42/Aß40 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 Aß42/Aß40 remained low and predicted cognitive decline in both CU and CI individuals. Among SAMS CU, plasma Aß42/Aß40 was associated with poorer hippocampal-dependent memory and elevated tau accumulation.Lumipulse plasma Aß42/Aß40 is a scalable assay for detection of cerebral Aß and prediction of risk for cognitive decline across the AD continuum.Lumipulse plasma amyloid beta (Aß)42/Aß40 exhibited high accuracy in detecting amyloid positivity. Plasma amyloid-positive (Aß+) individuals exhibited stability of Aß42/Aß40 over time. Plasma Aß42/Aß40 predicted future cognitive decline across the Alzheimer's disease (AD) spectrum. Plasma Aß42/Aß40 was sensitive to memory and tau burden in clinically unimpaired older adults.

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