Amyloid plaques are composed primarily of amyloid-beta (Aβ) peptides derived from proteolytic cleavage of amyloid precursor protein (APP) and are considered to play a pivotal role in Alzheimer's disease (AD) pathogenesis. Presently, AD is diagnosed after the onset of clinical manifestations. With the arrival of novel therapeutic agents for treatment of AD, there is an urgent need for biomarkers to detect early stages of AD. Measurement of plasma Aβ has been suggested as an inexpensive and non-invasive tool to diagnose AD and to monitor Aβ modifying therapies. However, the majority of cross-sectional studies on plasma Aβ levels in humans have not shown differences between individuals with AD compared to controls. Similarly, cross-sectional studies of mouse plasma Aβ have yielded inconsistent trends in different mouse models. However, longitudinal studies appear to be more promising in humans. Recently, efforts to modify plasma Aβ levels using modulators have shown some promise. In this review, we will summarize the present data on plasma Aβ in humans and mouse models of AD. We will discuss the potential of modulators of Aβ levels in plasma, including antibodies and insulin, and the challenges associated with measuring plasma Aβ. Modulators of plasma Aβ may provide an important tool to optimize plasma Aβ levels and may improve the diagnostic potential of this approach.
- Alzheimer's disease
- Transgenic mouse model of AD
ASJC Scopus subject areas
- Molecular Medicine
- Cellular and Molecular Neuroscience