Biological and methodological complexities of beta-amyloid peptide: Implications for Alzheimer's disease research

Although controversial, the amyloid cascade hypothesis remains central to the Alzheimer's disease (AD) field and posits amyloid-beta (A beta) as the central factor initiating disease onset. In recent years, there has been an increase in emphasis on studying the role of low molecular weight aggregates, such as oligomers, which are suggested to be more neurotoxic than fibrillary A beta. Other A beta isoforms, such as truncated A beta, have also been implicated in disease. However, developing a clear understanding of AD pathogenesis has been hampered by the complexity of A beta biochemistry in vitro and in vivo. This review explores factors contributing to the lack of consistency in experimental approaches taken to model A beta aggregation and toxicity and provides an overview of the different techniques available to analyse A beta, such as electron and atomic force microscopy, nuclear magnetic resonance spectroscopy, dye-based assays, size exclusion chromatography, mass spectrometry and SDS-PAGE. The review also explores how different types of A beta can influence A beta aggregation and toxicity, leading to variation in experimental outcomes, further highlighting the need for standardisation in A beta preparations and methods used in current research.

Automated summary

This article discusses the role of amyloid in Alzheimer's disease, explores factors leading to inconsistency in research methods, and analyzes different techniques for studying A beta. The study further underscores the need for standardization in A beta preparations and methods in current research.