Effects of apolipoprotein E isoform, sex, and diet on insulin BBB pharmacokinetics in mice

Elizabeth M. Rhea, Kim Hansen, Sarah Pemberton, Eileen Ruth S. Torres, Sarah Holden, Jacob Raber, William A. Banks

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Age, apolipoprotein E (apoE) isoform, sex, and diet can independently affect the risk for the development of Alzheimer’s disease (AD). Additionally, synergy between some of these risk factors have been observed. However, the relation between the latter three risk factors has not been investigated. Central nervous system (CNS) insulin resistance is commonly involved in each of these risk factors. CNS insulin is primarily derived from the periphery in which insulin must be transported across the blood–brain barrier (BBB). Additionally, insulin can bind the brain endothelial cell to affect intracellular signaling. Therefore, we hypothesized CNS access to insulin could be affected by the combination of apoE isoform, sex, and diet. We analyzed insulin BBB pharmacokinetics in aged apoE targeted replacement (E3 and E4) male and female mice on a low-fat and high-fat diet. There were differences within males and females due to apoE genotype and diet in insulin interactions at the BBB. These sex-, diet-, and apoE isoform-dependent differences could contribute to the cognitive changes observed due to altered CNS insulin signaling.

Original languageEnglish (US)
Article number18636
JournalScientific Reports
Volume11
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • General

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