Clusterin accumulates in synapses in Alzheimer's disease and is increased in apolipoprotein E4 carriers. Issue 1 (24th June 2019)

• Record Type: Journal Article
• Authors: Jackson, Rosemary J; Rose, Jamie; Tulloch, Jane; Henstridge, Chris; Smith, Colin; Spires-Jones, Tara L
• Is Part Of: Brain communications. Volume 1:Issue 1(2019)
• Publication Date: 2019-06-24
• Subjects: Alzheimer -- synapse -- clusterin -- apolipoprotein E -- array tomography; 616
• DOI: 10.1093/braincomms/fcz003
• Languages: English
• ISSNs: 2632-1297

Abstract

Abstract : Jackson and colleagues observe that clusterin accumulates in synapses in human Alzheimer's disease brain tissue, and that this accumulation is increased in people carrying the Alzheimer's disease risk gene apolipoprotein E4. These data use high-resolution imaging to link two genetic risk factors with amyloid-mediated synapse degeneration in Alzheimer's disease. Abstract: One of the major challenges in developing effective therapeutic strategies for Alzheimer's disease is understanding how genetic risk factors contribute to neurodegeneration. The apolipoprotein epsilon 4 isoform ( APOE4 ) and variants in the Clusterin ( CLU ) gene (also known as apolipoprotein J) are associated with increased risk of developing Alzheimer's. Our previous work demonstrated that APOE4 exacerbates synapse degeneration and synaptic accumulation of toxic oligomeric amyloid beta in human Alzheimer's and mouse models of disease. Here, we observe clusterin in synapses in human Alzheimer's disease brain. The percentage of synapses containing clusterin is higher in APOE4 carriers than APOE3 carriers. Furthermore, we observe oligomeric amyloid beta accumulation within synapses containing clusterin which is also higher in APOE4 carriers. These data link two genetic risk factors with synapse degeneration in Alzheimer's and support a potential role for clusterin working with APOE in causing synaptic damage. Graphical Abstract: