Andreas Giannisis (Sweden)
Stockholm University
Department of Biochemistry & Biophysics
My name is Andreas Giannisis, and I am from Greece. Currently, I am a 3rd year Ph.D. student at the Department of Biochemistry and Biophysics, at Stockholm University, under the project: ‘‘Relevance of a peripheral apolipoprotein E linked phenotype to neurodegeneration’’, having Professor Henrietta Nielsen as my supervisor. I hold a bachelor’s degree in chemistry from the Department of Chemistry, at the University of Ioannina, Greece, and a master’s degree in Neurochemistry with Molecular Neurobiology from the Department of Biochemistry and Biophysics, at Stockholm University, Sweden.

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 Conference Calendar

A LIVER APOE4 GENOTYPE IS LINKED TO HIGHER LEVELS OF HEPATIC CATHEPSIN-D

Session Name
0740 - APOE: MECHANISMS AND TREATMENT STRATEGIES 1 (ID 37)
Session Type
SYMPOSIUM
Date
Thu, 17.03.2022
Session Time
02:45 PM - 04:45 PM
Room
ONSITE: 112
Lecture Time
03:15 PM - 03:30 PM
Presenter

Abstract

Aims

Low plasma levels of apolipoprotein E (apoE) were previously linked to a higher risk of Alzheimer’s disease (AD).Plasma apoE is mainly derived from the liver and APOEε4-carriers frequently exhibit lower levels than non-carriers.We speculate that a liver APOEε4-phenotype contributes to the increased risk of AD.The liver is essential to various physiological processes including lipid-metabolism and peripheral amyloid-β (Aβ) clearance.Previous studies have shown that Aβ-degrading enzymes in the liver are altered in AD however;a potential contribution of APOEε4 genotype to these findings has not been investigated.

Methods

Pellets of primary human hepatocytes (total of:n=69) isolated from liver tissues acquired through liver transplantation were APOE genotyped using real-time polymerase-chain-reaction.Protein levels of Aβ-degrading enzymes cathepsin-D (CatD), insulin-degrading enzyme (IDE) and neprilysin were assessed using western blot in RIPA buffered cell lysates.

Results

Regardless of APOEε4 genotype, higher levels of IDE were linked to higher levels of both CatD (Spearman’s-ρ=0.404,p=0.001) and neprilysin (Spearman’s-ρ=0.501,p<0.001).These associations remained even after separating the subjects based on their APOEε4 allele status.Interestingly, hepatocytes isolated from APOEε4-carriers (n=52) exhibited 73% higher levels of CatD compared to hepatocytes from non-carriers (n=17) (p=0.004) with the highest levels found in APOEε4 homozygous carriers.Presence of APOEε4 had no effect on the levels of neprilysin and IDE.

Conclusions

The significant associations between neprilysin, IDE and CatD might indicate that APOEε4 genotype affects the Aβ-degrading enzymes neprilysin and IDE through CatD.Previous studies have also proposed that CatD can degrade apoE and the observed APOEε4-dependent increase in this enzyme may help explain the lower plasma apoE levels documented in APOEε4 subjects.

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