Biological and methodological complexities of beta‐amyloid peptide: Implications for Alzheimer's disease research. Issue 4 (24th November 2021)

• Record Type: Journal Article
• Authors: Matuszyk, Martyna M.; Garwood, Claire J.; Ferraiuolo, Laura; Simpson, Julie E.; Staniforth, Rosemary A.; Wharton, Stephen B.
• Is Part Of: Journal of neurochemistry. Volume 160:Issue 4(2022)
• Page Start: 434
• Page End: 453
• Publication Date: 2021-11-24
• Subjects: Alzheimer's -- Alzheimer's disease -- amyloid beta -- Aβ -- fibrils -- oligomers -- SDS‐PAGE, sodium dodecyl Sulphate‐polyacrylamide gel electrophoresis; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.15538
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: Although controversial, the amyloid cascade hypothesis remains central to the Alzheimer's disease (AD) field and posits amyloid‐beta (Aβ) 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 toxicity and provides an overview of the different techniques available to analyse Aβ, 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 Aβ can influence Aβ aggregation and toxicity, leading to variation in experimental outcomes, further highlighting the need for standardisation in Aβ preparations and methods used in current research. Abstract : Amyloid‐beta (Aβ) 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 field of Aβ biochemistry in the context of AD pathology.