Ruling in, ruling out: the clinical utility of plasma biomarkers in diagnosis of Alzheimer’s disease

Abstract

Introduction On May 16, 2025, the US FDA approved the first blood-based test for amyloid plaques — the Lumipulse G pTau217/β-Amyloid 1–42 Plasma Ratio — for adults aged 55 years and older who are exhibiting signs and symptoms of Alzheimer disease (AD) (1). The presence of amyloid plaques has long been recognized as the earliest pathological indicator of looming cognitive decline and functional impairment associated with AD. First documented by Alois Alzheimer in 1906 (2), the field of AD research was hampered by limitations in their detectability: amyloid plaques could only be identified at autopsy. Nearly 100 years later, a radiotracer known as the Pittsburgh Compound B (PiB) was the first approved in vivo approach for visualizing and quantifying amyloid plaques via PET imaging (3). The challenges, costs, and lack of availability of PET led to development of cerebrospinal fluid (CSF) assays, with the first approval occurring in 2022 (4). The development of a blood-based test for AD pathology has long been an aim of the field; the possibility was first suggested in 1984 by Glenner and Wong, who isolated the amyloid protein (5). The successful development of a blood-based assay has the potential to transform screening for AD pathology, expanding accessibility and allowing for application in nonspecialized clinical practice. Diagnosing AD can be difficult owing to variable clinical presentation […]