The effects of apolipoprotein E genotype, α-synuclein deficiency, and sex on brain synaptic and Alzheimer's disease–related pathology

Roni Bar, Anat Boehm-Cagan, Ishai Luz, Yarden Kleper-Wall, Daniel M. Michaelson

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction Alzheimer's disease (AD) and synucleinopathies share common pathological mechanisms. Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for AD, also increases the risk for dementia in pure synucleinopathies. We presently examined the effects of α-synuclein deficiency (α-syn−/−) and sex on apoE4-driven pathologies. Methods AD-related, synaptic, and vascular markers were analyzed in female and male α-syn−/− and α-syn+/+ apoE4, apoE3, and apoE3/E4 mice. Results ApoE4 was hypolipidated, and this effect was unchanged by α-syn−/− and sex. The levels of synaptic markers were lower, and the levels of AD-related parameters were higher in female α-syn−/− apoE4 mice compared with the corresponding apoE3 mice. By comparison, apoE4 had small effects on the AD parameters of male and female α-syn+/+ apoE4 mice. Discussion Although α-syn−/− does not affect the upstream lipidation impairment of apoE4, it acts as a “second hit” enhancer of the subsequent apoE4-driven pathologies.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume10
DOIs
StatePublished - 2018

Keywords

  • Alzheimer's disease
  • Apolipoprotein E4 (apoE4)
  • Sex
  • apoE-targeted replacement mice
  • α-Synuclein deficiency

Fingerprint

Dive into the research topics of 'The effects of apolipoprotein E genotype, α-synuclein deficiency, and sex on brain synaptic and Alzheimer's disease–related pathology'. Together they form a unique fingerprint.

Cite this