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The combination of immunoprecipitation (IP) with MALDI-TOF MS resulted in IP-MALDI-MS, an analytical technique that led to the first successful detection of plasma amyloid-β (Aβ) by mass spectrometry. This helped to identify plasma APP669–711/Aβ1–42 ratio, a novel biomarker that correlates with amyloid PET. Samples from Japan and Australia 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 both. With advances in disease-modifying drugs, blood-based biomarkers increase in value due to their role in screening subjects and drug effects, and as adjuncts in the diagnosis of AD.