Moving fluid biomarkers for Alzheimer's disease from research tools to routine clinical diagnostics

Abstract

Four fluid-based biomarkers have been developed into diagnostic tests for Alzheimer's disease (AD) pathology: the ratio of 42 to 40 amino acid-long amyloid β, a marker of plaque pathology; total-tau and phosphorylated tau, markers of AD-related changes in tau metabolism and secretion; and neurofilament light, a marker of neurodegeneration. When measured in cerebrospinal fluid, these biomarkers can be used in clinical practice to support a diagnosis of mild cognitive impairment or dementia due to AD. Recently, technological breakthroughs have made it possible to measure them in standard blood samples as well. Here, we give an updated account of the current state of the fluid-based AD biomarker research field. We discuss how the new blood tests may be used in research and clinical practice, and what role they may play in relation to more established diagnostic tests, such as CSF biomarkers and amyloid and tau positron emission tomography, to facilitate the effective implementation of future disease-modifying therapies.

Keywords: Alzheimer’s disease; Biomarkers; CSF; Clinical diagnostics; Plasma; Research.

Fig. 1

Timeline for blood biomarker developments during the last decade. Abbreviations: Simoa, Single molecule array; Aβ42, the 42 amino acid form of amyloid β; T-tau, total-tau; IP-LC/MS, immunoprecipitation liquid chromatography-mass spectrometry; IP-MALDI, immunoprecipitation matrix-assisted laser desorption/ionization; Aβ40, the 40 amino acid form of amyloid β; NfL, neurofilament light; P-tau181, tau phosphorylated at amino acid 181; P-tau217, tau phosphorylated at amino acid 217; ECL, electrochemiluminescence