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Breaking the Cycle, Cholesterol Cycling, and Synapse Damage in Response to Amyloid-ß

Bate, C


C Bate


Soluble amyloid-β (Aβ) oligomers, a key driver of pathogenesis in Alzheimer disease, bind to cellular prion proteins (PrPC) expressed on synaptosomes resulting in increased cholesterol concentrations, movement of cytoplasmic phospholipase A2 (cPLA2) to lipid rafts and activation of cPLA2. The formation of Aβ-PrPC-cPLA2 complexes was controlled by the cholesterol ester cycle. Thus, Aβ activated cholesterol ester hydrolases which released cholesterol from stores of cholesterol esters; the increased cholesterol concentrations stabilised Aβ-PrPC-cPLA2 complexes. Conversely, cholesterol esterification reduced cholesterol concentrations causing the dispersal of Aβ-PrPC-cPLA2. In cultured neurons, the cholesterol ester cycle regulated Aβ-induced synapse damage; inhibition of cholesterol ester hydrolases protected neurons, whereas inhibition of cholesterol esterification increased the Aβ-induced synapse damage. Here, I speculate that a failure to deactivate signalling pathways can lead to pathology. Consequently, the esterification of cholesterol is a key factor in the dispersal of Aβ-induced signalling platforms and synapse degeneration.


Bate, C. (2017). Breaking the Cycle, Cholesterol Cycling, and Synapse Damage in Response to Amyloid-ß. Journal of Experimental Neuroscience, 11,

Journal Article Type Article
Acceptance Date Sep 1, 2017
Publication Date Dec 6, 2017
Deposit Date Jan 25, 2018
Publicly Available Date Jan 25, 2018
Journal Journal of Experimental Neuroscience
Publisher SAGE Publications
Peer Reviewed Peer Reviewed
Volume 11
Public URL


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