Ultrasensitive Detection of Plasma Amyloid-β as a Biomarker for Cognitively Normal Elderly Individuals at Risk of Alzheimer’s Disease

Abstract

Background:

Aberrant amyloid-β (Aβ) deposition in the brain occurs two decades prior to the manifestation of Alzheimer’s disease (AD) clinical symptoms and therefore brain Aβ load measured using PET serves as a gold standard biomarker for the early diagnosis of AD. However, the uneconomical nature of PET makes blood markers, that reflect brain Aβ deposition, attractive candidates for investigation as surrogate markers.

Objective:

Investigation of plasma Aβ as a surrogate marker for brain Aβ deposition in cognitively normal elderly individuals.

Methods:

Plasma Aβ₄₀ and Aβ₄₂ concentrations were measured using the ultrasensitive Single Molecule Array (Simoa) assay in 95 cognitively normal elderly individuals, who have all undergone PET to assess brain Aβ deposition. Based on the standard uptake value ratios (SUVR) obtained from PET imaging, using the tracer ¹⁸F-Florbetaben, plasma Aβ was compared between 32 participants assessed to have low brain Aβ load (Aβ–, SUVR <1.35) and 63 assessed to have high brain Aβ load (Aβ+, SUVR ≥1.35).

Results:

Plasma Aβ₄₂/Aβ₄₀ ratios were lower in the Aβ+ group compared to the Aβ–group. Plasma Aβ₄₀ and Aβ₄₂ levels were not significantly different between Aβ–and Aβ+ groups, although a trend of higher plasma Aβ₄₀ was observed in the Aβ+ group. Additionally, plasma Aβ₄₂/Aβ₄₀ ratios along with the known AD risk factors, age and APOE ɛ4 status, resulted in Aβ+ participants being distinguished from Aβ–participants based on an area under the receiver operating characteristic curve shown to be 78%.

Conclusion:

Plasma Aβ ratios in this study are a potential biomarker for brain Aβ deposition and therefore, for preclinical AD. However, this method to measure plasma Aβ needs further development to increase the accuracy of this promising AD blood biomarker.