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

Summary

This review discusses the development and potential clinical application of four fluid biomarkers (Aβ42/40, t-tau, p-tau, NfL) for Alzheimer's disease, highlighting their measurement in blood and their role alongside existing diagnostic methods to support the use of future disease-modifying therapies.

Key findings

• CSF biomarkers (Aβ42/40, t-tau, p-tau, NfL) are established diagnostic tools for AD.
• Blood-based versions of these biomarkers are now available.
• Blood biomarkers offer a less invasive alternative to CSF analysis.
• These biomarkers are essential for the effective use of emerging AD treatments.

Methods

• Measurement of Aβ42/40 ratio in cerebrospinal fluid (CSF) and blood.
• Measurement of total-tau (t-tau) and phosphorylated tau (p-tau) in CSF and blood.
• Measurement of neurofilament light (NfL) in CSF and blood.
• Comparison of fluid biomarkers with CSF biomarkers and PET imaging.

Limitations

• The abstract does not detail specific limitations of the reviewed studies.
• The focus is on diagnostic potential, not necessarily therapeutic efficacy.
• Implementation challenges for routine clinical use are not fully elaborated.
• The paper is a review, thus limitations are inherent to the studies it synthesizes.

Applications

• Supporting clinical diagnosis of mild cognitive impairment or dementia due to AD.
• Monitoring disease progression.
• Assessing response to disease-modifying therapies.
• Facilitating clinical trials for AD therapeutics.