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Shimadzu Review 78[3・4] (2021)
Abstract
Alzheimer’s disease (AD) accounts for around 60 to 70% of dementia cases and is a problem faced by societies throughout the world. Clinical trials of disease-modifying drugs target subjects with early-stage AD, hence blood-based biomarkers are needed for subject screening. We combined immunoprecipitation (IP) with MALDI-TOF MS to develop IP-MALDI-MS, an analytical technique that resulted in the first successful detection of plasma amyloid β (Aβ) by mass spectrometry. This technique was used to identify plasma APP669–711/Aβ1–42 ratio, a novel biomarker that correlates with amyloid PET. Analysis of samples from subjects in Japan and Australia also revealed a high degree of concordance between amyloid PET and plasma APP669–711/Aβ1–42 ratio, plasma Aβ1–40/Aβ1–42 ratio, and a combination of these two biomarkers (a composite biomarker). As advances are made in disease-modifying drugs, blood-based biomarkers will become increasingly valuable due to their potential role for screening subjects and monitoring drug effects in clinical trials, and as adjuncts in the diagnosis of AD in clinical practice.
Koichi Tanaka Mass Spectrometry Research Laboratory, Shimadzu Corporation, Kyoto, Japan
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