Amyloid-Related Biomarkers for Alzheimers Disease

Niels      Andreasen; Henrik      Zetterberg

doi:10.2174/092986708783955572

Abstract

Alzheimers disease (AD) is an age-related disorder that causes brain damage resulting in progressive cognitive impairment and death. Three decades of progress have given us a detailed understanding of the underlying molecular mechanisms. Over the past 10 years, this knowledge has translated into a range of targets for therapy, the most promising of which is amyloid β (Aβ). An imbalance between the production and clearance of Aβ is thought by many to represent the earliest event in the pathogenesis of AD. Aβ is known to be subject to oligomerisation, a process that increases its synaptotoxicity. The oligomers may aggregate further to proto-fibrils and fibrils, eventually forming senile plaques, the neuropathological hallmark of AD. In this article we review the key aspects of Aβ as a biomarker for AD, including its pathogenicity, the diagnostic performance of different Aβ assays in different settings, and the potential usefulness of Aβ as a surrogate marker for treatment efficacy in clinical trials of novel Aβ-targeting drugs.

Keywords: Alzheimer's disease, amyloid precursor protein, β-amyloid, biomarker, cerebrospinal fluid, plasma, positron emission tomography

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