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

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.

Modulation of Amyloid β-Induced Microglia Activation and Neuronal Cell Death by Curcumin and Analogues

“…Since Aβ oligomers are heterogeneous populations of polymorphic and non-covalent aggregates, their study is complicated and often leads to controversial results [12,50]. Over the years, Aβ aggregates and their toxicity have been studied using multiple techniques (e.g., SDS-PAGE, mass spectrometry, NMR spectroscopy, size exclusion chromatography, electron, and atomic force spectroscopy [51], dynamic and multiangle light scattering [52,53]) that can be subject to limitations or disadvantages. The use of CE for the detection and separation of soluble oligomeric species of Aβ peptides has been introduced by us [49].…”

Berberine: A Promising Treatment for Neurodegenerative Diseases

“…In Alzheimer’s disease mice, GFAP and neuron loss increased and neuronal nuclei (NeuN) decreased significantly. Studies have found that under pathological conditions, astrocytes are activated by Aβ to produce cytoinflammatory factors, complement, oxygen free radicals, etc., which then trigger inflammation, promote nerve cell damage and death, and ultimately aggravate Alzheimer’s disease ( Do et al, 2014 ; Matuszyk et al, 2021 ). The latest research shows that berberine significantly decreases the expression of GFAP in the Alzheimer’s disease mice hippocampus, indicating berberine inhibits the overexpression of astrocytes in Alzheimer’s disease mice.…”

Oxymatrine-mediated prevention of amyloid β-peptide-induced apoptosis on Alzheimer’s model PC12 cells: in vitro cell culture studies and in vivo cognitive assessment in rats

“…Amyloid β-peptide (Aβ25-35) is a bioactive component of Aβ peptide, it leads to oxidative stress, memory loss, and apoptotic effects in brain cells. Neurotoxic short Aβ25-35 peptide fragments affect the tissues of the neurons [6][7][8][9][10][11][12]. Present scenario, most of the scienti c experiments demonstrated that the aggregation of Aβ peptide causes oxidative stress-mediated necrosis in neuronal cells and develops AD.…”