Aß-Induced Alterations in Membrane Lipids Occur before Synaptic Loss Appears.

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 (Aß) species, generally known as amyloidosis. There are two major known human Aß species: Aß(1-40) and Aß(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 Aß 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 Aß species in the loss of active synapses and the dysregulation of membrane lipids in vitro. We showed that Aß(1-40) or Aß(1-42) treatment influences membrane lipids before synaptic loss appears and that the loss of active synapses is not dependent on the Aß 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.