Clusterin accumulates in synapses in Alzheimer’s disease and is increased in Apolipoprotein E4 carriers

Rosemary J. Jackson, Jamie Rose, Jane Tulloch, Christopher Henstridge, Colin Smith, Tara L. Spires-Jones (Lead / Corresponding author)

Research output: Contribution to journalArticle

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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 isoform epsilon 4 (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’sand mouse models of disease. Here we observe clusterin in synapses in human AD 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’sand support a potential role for clusterin working with APOE in causing synaptic damage.
Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalBrain Communications
DOIs
Publication statusPublished - 24 Jun 2019

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Clusterin
Apolipoprotein E4
Synapses
Alzheimer Disease
Apolipoproteins
Protein Isoforms
Amyloid
Poisons
Brain
Genes

Keywords

  • Alzheimer
  • synapse
  • clusterin
  • apolipoprotein E
  • array tomography

Cite this

Jackson, Rosemary J. ; Rose, Jamie ; Tulloch, Jane ; Henstridge, Christopher ; Smith, Colin ; Spires-Jones, Tara L. / Clusterin accumulates in synapses in Alzheimer’s disease and is increased in Apolipoprotein E4 carriers. In: Brain Communications. 2019 ; pp. 1-12.
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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 isoform epsilon 4 (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’sand mouse models of disease. Here we observe clusterin in synapses in human AD 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’sand support a potential role for clusterin working with APOE in causing synaptic damage.",
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Clusterin accumulates in synapses in Alzheimer’s disease and is increased in Apolipoprotein E4 carriers. / Jackson, Rosemary J.; Rose, Jamie; Tulloch, Jane; Henstridge, Christopher; Smith, Colin; Spires-Jones, Tara L. (Lead / Corresponding author).

In: Brain Communications, 24.06.2019, p. 1-12.

Research output: Contribution to journalArticle

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