Abstract
It is widely accepted that β-amyloid oligomers (Aβos) play a key role in the progression of Alzheimer’s disease (AD) by inducing neuron damage and cognitive impairment, but Aβos are highly heterogeneous in their size, structure and cytotoxicity, making the corresponding studies tough to carry out. Nevertheless, a number of studies have recently made remarkable progress in the describing the characteristics and pathogenicity of Aβos. We here review the mechanisms by which Aβos exert their neuropathogenesis for AD progression, including receptor binding, cell membrane destruction, mitochondrial damage, Ca2+ homeostasis dysregulation and tau pathological induction. We also summarize the characteristics and pathogenicity such as the size, morphology and cytotoxicity of dimers, trimers, Aβ*56 and spherical oligomers, and suggest that Aβos may play a different role at different phases of AD pathogenesis, resulting in differential consequences on neuronal synaptotoxicity and survival. It is warranted to investigate the temporal sequence of Aβos in AD human brain and examine the relationship between different Aβos and cognitive impairment.
Highlights
Alzheimer disease (AD) is a chronic neurodegenerative disease which imposes a heavy burden on families and society [1]
The neuropathological profiles of AD are mainly manifested as the extracellular senile plaques aggregated by β-amyloid (Aβ), and the formation of intracellular neurofibrillary tangles aggregated by hyperphosphorylated tau protein [2]
Β2 -AR can promote tau protein phosphorylation through the β2 -adrenergic receptor (β2 -AR)-protein kinase A (PKA)-JNK signaling pathway [40]. These results demonstrate that β2 -AR may have an important effect on AD pathogenesis
Summary
Alzheimer disease (AD) is a chronic neurodegenerative disease which imposes a heavy burden on families and society [1]. Aβ has normal physiological function and maintains a low concentration in vivo [3], factors such as aging, oxidative stress and gene mutation cause the disruption of Aβ homeostasis, resulting in Aβ accumulation and aggregation, formation of oligomers and fibers, and plaque deposits in brains [4]. Aβ oligomers (Aβos) are the most neurotoxic aggregates and play a critical role in the occurrence and development of AD by causing functional neuron death, cognitive damage, and dementia. Aβos have been extracted and characterized by various methods, and remarkable progress has been made in the mechanism of pathogenesis. We introduce the neurotoxic mechanisms of Aβos, and review the properties of Aβos with different size, conformation and neurotoxicity
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