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Biological markers of amyloid β-related mechanisms in Alzheimer's disease

2009; Elsevier BV; Volume: 223; Issue: 2 Linguagem: Inglês

10.1016/j.expneurol.2009.09.024

1090-2430

Harald Hampel, Yong Shen, Dominic M. Walsh, Paul Aisen, Les Shaw, Henrik Zetterberg, John Q. Trojanowski, Kaj Blennow,

Cholinesterase and Neurodegenerative Diseases

Recent research progress has given detailed knowledge on the molecular pathogenesis of Alzheimer's disease (AD), which has been translated into an intense, ongoing development of disease-modifying treatments. Most new drug candidates are targeted on inhibiting amyloid β (Aβ) production and aggregation. In drug development, it is important to co-develop biomarkers for Aβ-related mechanisms to enable early diagnosis and patient stratification in clinical trials, and to serve as tools to identify and monitor the biochemical effect of the drug directly in patients. Biomarkers are also requested by regulatory authorities to serve as safety measurements. Molecular aberrations in the AD brain are reflected in the cerebrospinal fluid (CSF). Core CSF biomarkers include Aβ isoforms (Aβ40/Aβ42), soluble APP isoforms, Aβ oligomers and β-site APP-cleaving enzyme 1 (BACE1). This article reviews recent research advances on core candidate CSF and plasma Aβ-related biomarkers, and gives a conceptual review on how to implement biomarkers in clinical trials in AD.