Potential Utility of Plasma P-Tau and Neurofilament Light Chain as Surrogate Biomarkers for Preventive Clinical Trials

Review Medicine, Research & Experimental

Blood-based biomarkers for Alzheimer's disease

Antoine Leuzy et al.

Summary: Blood-based biomarkers are playing an increasing role in the diagnosis and research of neurodegenerative disorders like Alzheimer's disease. Biomarkers such as plasma P-tau and NfL show promising potential for detection and monitoring of these diseases.

EMBO MOLECULAR MEDICINE (2022)

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Review Clinical Neurology

Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility

Thomas K. Karikari et al.

Summary: This article summarizes the performance of blood phosphorylated tau biomarkers in the context of Alzheimer disease (AD) and discusses the related ethical, analytical, and clinical challenges. It highlights the potential of blood biomarkers as first-line diagnostic and prognostic tools, but emphasizes the need to address outstanding ethical, clinical, and analytical challenges, and standardize inter-laboratory and inter-assay measurements.

NATURE REVIEWS NEUROLOGY (2022)

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Article Clinical Neurology

Association of Donanemab Treatment With Exploratory Plasma Biomarkers in Early Symptomatic Alzheimer Disease A Secondary Analysis of the TRAILBLAZER-ALZ Randomized Clinical Trial

Michael J. Pontecorvo et al.

Summary: Significant reductions in plasma biomarkers pTau(217) and glial fibrillary acidic protein were observed following donanemab treatment in patients with early symptomatic Alzheimer disease. These easily accessible plasma biomarkers might provide additional evidence of Alzheimer disease pathology change through anti-amyloid therapy. Usefulness in assessing treatment response will require further evaluation.

JAMA NEUROLOGY (2022)

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Article Clinical Neurology

Longitudinal Associations of Blood Phosphorylated Tau181 and Neurofilament Light Chain With Neurodegeneration in Alzheimer Disease

Alexis Moscoso et al.

Summary: This study found that plasma p-tau181 could serve as a marker for predicting and monitoring neurodegeneration and cognitive decline, with greater AD specificity compared to plasma NfL, holding important implications for monitoring AD progression in clinical practice and treatment trials.

JAMA NEUROLOGY (2021)

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Article Clinical Neurology

A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer's disease with lecanemab, an anti-Aβ protofibril antibody

Chad J. Swanson et al.

Summary: BAN2401-G000-201 trial aimed to establish the effective dose and observe the treatment effect. While not meeting the primary endpoint at 12 months, results at 18 months demonstrated reduction in brain amyloid and improvement across multiple clinical and biomarker endpoints.

ALZHEIMERS RESEARCH & THERAPY (2021)

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Review Biochemistry & Molecular Biology

Biomarkers for neurodegenerative diseases

Oskar Hansson

Summary: Biomarkers for neurodegenerative diseases play a crucial role in improving diagnostic workup and therapy monitoring, with emerging blood-based markers and discussions on their implementation in clinical practice and trials.

NATURE MEDICINE (2021)

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Article Multidisciplinary Sciences

Plasma biomarkers of Alzheimer's disease improve prediction of cognitive decline in cognitively unimpaired elderly populations

Nicholas C. Cullen et al.

Summary: Plasma biomarkers of amyloid, tau, and neurodegeneration (ATN) can predict clinical deterioration in cognitively unimpaired elderly individuals. A combination of these biomarkers in plasma can reduce the required sample size in clinical trials, making them more feasible and cost-effective while improving efficacy.

NATURE COMMUNICATIONS (2021)

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Article Clinical Neurology

Alzheimer's disease drug development pipeline: 2021

Jeffrey Cummings et al.

Summary: Overall, the study highlights the urgent need for new treatments for Alzheimer's disease, and shows that a diverse range of drugs targeting the biology of AD are being explored in clinical trials. Biomedical biomarkers are also being increasingly used in these trials to assess effectiveness.

ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS (2021)

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Article Clinical Neurology