Opposing Roles of apolipoprotein E in aging and neurodegeneration

Eloise Hudry, Jacob Klickstein, Claudia Cannavo, Rosemary Jackson, Alona Muzikansky, Sheetal Gandhi, David Urick, Taylie Sargent, Lauren Wrobleski, Allyson D. Roe, Steven S. Hou, Kishore V. Kuchibhotla, Rebecca A. Betensky, Tara Spires-Jones, Bradley T. Hyman

Research output: Contribution to journalArticle

Abstract

Apolipoprotein E (APOE) effects on brain function remain controversial. Removal of APOE not only impairs cognitive functions but also reduces neuritic amyloid plaques in mouse models of Alzheimer's disease (AD). Can APOE simultaneously protect and impair neural circuits? Here, we dissociated the role of APOE in AD versus aging to determine its effects on neuronal function and synaptic integrity. Using two-photon calcium imaging in awake mice to record visually evoked responses, we found that genetic removal of APOE improved neuronal responses in adult APP/PSEN1 mice (8-10 mo). These animals also exhibited fewer neuritic plaques with less surrounding synapse loss, fewer neuritic dystrophies, and reactive glia. Surprisingly, the lack of APOE in aged mice (18-20 mo), even in the absence of amyloid, disrupted visually evoked responses. These results suggest a dissociation in APOE's role in AD versus aging: APOE may be neurotoxic during early stages of amyloid deposition, although being neuroprotective in latter stages of aging.

Original languageEnglish (US)
JournalLife science alliance
Volume2
Issue number1
DOIs
StatePublished - Feb 1 2019

ASJC Scopus subject areas

  • Ecology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Plant Science
  • Health, Toxicology and Mutagenesis

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    Hudry, E., Klickstein, J., Cannavo, C., Jackson, R., Muzikansky, A., Gandhi, S., Urick, D., Sargent, T., Wrobleski, L., Roe, A. D., Hou, S. S., Kuchibhotla, K. V., Betensky, R. A., Spires-Jones, T., & Hyman, B. T. (2019). Opposing Roles of apolipoprotein E in aging and neurodegeneration. Life science alliance, 2(1). https://doi.org/10.26508/lsa.201900325