Biological and methodological complexities of beta ‐amyloid peptide: Implications for Alzheimer’s disease research

Amyloid-beta (A β) hypothesis drives the notion that Aβ peptide is a central player in Alzheimer's disease (AD) onset and/ or progression. However, it remains difficult to investigate Aβ in vitro due to differences in published protocols describing varying methods of peptide preparations. This is especially true as protocols may vary depending on whether toxic Aβ oligomers (as well as associated isoforms) or plaque- forming Aβ fibrils are investigated. Due to the biochemical and structural differences in both peptide species, the methods of peptide characterisation also vary, further complicating the fie ld of Aβ biochemistry in the context of AD pathology. AbstractAlthough controversial, the amyloid cascade hypothesis remains central to the Alzheimer's disease (AD) field and posits amyloid-beta (A β) 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 Aβ. Other Aβ isoforms, such as truncated Aβ, have also been implicated in disease. However, developing a clear understanding of AD pathogenesis has been hampered by the complexity of Aβ biochemistry in vitro and in vivo. This review explores factors contributing to the lack of consistency in experimental approaches taken to model Aβ aggregation and to xicity and provides an overview of the different techniques available to analyse A...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: REVIEW ARTICLE Source Type: research