Abstract
Loss of active synapses and alterations in membrane lipids are crucial events in physiological aging as well as in neurodegenerative disorders. Both are related to the abnormal aggregation of amyloid-beta (Aβ) species, generally known as amyloidosis. There are two major known human Aβ species: Aβ(1–40) and Aβ(1–42). However, which of these species have more influence on active synapses and membrane lipids is still poorly understood. Additionally, the time-dependent effect of Aβ species on alterations in membrane lipids of hippocampal neurones and glial cells remains unknown. Therefore, our study contributes to a better understanding of the role of Aβ species in the loss of active synapses and the dysregulation of membrane lipids in vitro. We showed that Aβ(1–40) or Aβ(1–42) treatment influences membrane lipids before synaptic loss appears and that the loss of active synapses is not dependent on the Aβ species. Our lipidomic data analysis showed early changes in specific lipid classes such as sphingolipid and glycerophospholipid neurones. Our results underscore the potential role of lipids as a possible early diagnostic biomarker in amyloidosis-related disorders.
Highlights
Amyloidosis is used as an umbrella term for rare, serious diseases caused by the deposit of misfolded proteins
In this study, using different quantitative cellular techniques in different Aβ-treated primary brain cells, we showed for the first time that lipid profiles change after treatment and before synaptic loss was observed
We showed that human Aβ species exogenously applied to primary neurones and glial cells influence the numbers of active synapses and led to lipid alterations in a time-dependent manner
Summary
Amyloidosis is used as an umbrella term for rare, serious diseases caused by the deposit of misfolded proteins. In brain tissue, it is characterised by the accumulation of amyloid-beta (Aβ), such as occurs in Alzheimer’s disease (AD) [1]. In vitro and in vivo studies have demonstrated that soluble Aβ species accumulate at the synaptic sites, resulting in disrupted synaptic plasticity and long-term potential [5,6,7,8]. As has been demonstrated in vitro and in vivo, Aβ species have different influences on the pre- and postsynaptic densities dependent on the
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