Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide

Tadafumi Hashimoto, Alberto Serrano-Pozo, Yukiko Hori, Kenneth W Adams, Shuko Takeda, Adrian Olaf Banerji, Akinori Mitani, Daniel Joyner, Diana H Thyssen, Brian J Bacskai, Matthew P Frosch, Tara L Spires-Jones, Mary Beth Finn, David M Holtzman, Bradley T Hyman

Research output: Contribution to journalArticlepeer-review

Abstract

Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder causing dementia. Massive deposition of amyloid β peptide (Aβ) as senile plaques in the brain is the pathological hallmark of AD, but oligomeric, soluble forms of Aβ have been implicated as the synaptotoxic component. The apolipoprotein E ε 4 (apoE ε4) allele is known to be a genetic risk factor for developing AD. However, it is still unknown how apoE impacts the process of Aβ oligomerization. Here, we found that the level of Aβ oligomers in APOE ε4/ε4 AD patient brains is 2.7 times higher than those in APOE ε3/ε3 AD patient brains, matched for total plaque burden, suggesting that apoE4 impacts the metabolism of Aβ oligomers. To test this hypothesis, we examined the effect of apoE on Aβ oligomer formation. Using both synthetic Aβ and a split-luciferase method for monitoring Aβ oligomers, we observed that apoE increased the level of Aβ oligomers in an isoform-dependent manner (E2
Original languageEnglish
Pages (from-to)15181-92
Number of pages12
JournalJournal of Neuroscience
Volume32
Issue number43
DOIs
Publication statusPublished - 24 Oct 2012

Keywords

  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Analysis of Variance
  • Apolipoprotein E2
  • Apolipoprotein E3
  • Apolipoprotein E4
  • Astrocytes
  • Brain
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Green Fluorescent Proteins
  • HEK293 Cells
  • Humans
  • Lipid Metabolism
  • Male
  • Morpholinos
  • Peptide Fragments
  • Protein Isoforms
  • Transfection

Fingerprint

Dive into the research topics of 'Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide'. Together they form a unique fingerprint.

Cite this