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32 - Development of Fluid Biomarkers for Alzheimer’s Disease

from Section 4 - Imaging and Biomarker Development in Alzheimer’s Disease Drug Discovery

Published online by Cambridge University Press:  03 March 2022

By
Kaj Blennow
Edited by
Jeffrey Cummings ,
Jefferson Kinney  and
Howard Fillit
Jeffrey Cummings
Affiliation:
University of Nevada, Las Vegas
Jefferson Kinney
Affiliation:
University of Nevada, Las Vegas
Howard Fillit
Affiliation:
Alzheimer’s Drug Discovery Foundation
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Summary

There has been a rapid development of cerebrospinal fluid (CSF) and also blood biomarkers in the field of Alzheimer’s disease (AD) clinical research and drug development. Clinical research studies support that the core AD CSF biomarkers amyloid beta (Aβ42 and Aβ42/40 ratio), total-tau (t-tau), and hyperphosphorylated tau (p-tau) reflect key elements of AD pathophysiology. The “Alzheimer CSF profile”, decreased Aβ42/40 ratio together with increased t-tau and p-tau, has high diagnostic value, and high concordance with amyloid PET. These biomarkers have undergone thorough standardization and are today available on fully automated laboratory analyzers. Recent technical developments in the field of ultrasensitive immunoassays and mass spectrometry methods also allow for measurement of these AD biomarkers in blood samples. Blood neurofilament light may also be a biomarker to grade axonal degeneration in AD and other neurodegenerative disorders. These biomarkers are important in AD drug development, for screening tools and diagnostic markers, and the verification of target engagement of candidate molecules in early trials and identification of downstream drug effects in late-stage trials.

Keywords

Biomarkerscerebrospinal fluidamyloidtauneurofilament lightscreening toolsdiagnostic markers
Type
Chapter
Information
Alzheimer's Disease Drug Development
Research and Development Ecosystem
 , pp. 361 - 374
Publisher: Cambridge University Press
Print publication year: 2022

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