Proteomic analysis of mice expressing human ApoE demonstrates no differences in global protein solubility between APOE 3 and APOE 4 young mice

Abstract

Apolipoprotein E (ApoE) is a major lipid carrier protein. In humans, ApoE is expressed in three polymorphic isoforms, which are encoded by three different alleles APOE2, APOE3, and APOE4. In the brains of Alzheimer's disease (AD) patients, each one of these three allelic isoforms is found in several "isoelectric" protein isoforms (qPI), i.e. protein isoforms resulting from PTMs altering the net charge (q) of the polypeptide. AD is a complex disease in which multiple causes and several risk factors affect the onset and disease outcome. A major risk factor for AD is ApoE4; therefore, it is important to characterize the different ApoE qPIs. We have implemented a detergent-based method for isolation and quantitation of protein isoforms, and we found differences in the solubility of protein isoforms depending on the type of solvent used. In this manuscript, we describe these methods and applied them to young human-ApoE targeted replacement mice. Our results indicate that there are no significant differences in the hippocampus proteome of these mice as a function of the APOE genotype.

Insulin resistance and cognitive dysfunction

“…ApoE is a polymorphic protein with common variants known as E2, E3, and E4 that are encoded by the ε2, ε3, and ε4 alleles, respectively, with population frequencies of approximately 8, 77 and 15%, respectively [97][98][99]. ApoE4 has been confirmed as an important factor for dementia and progress of cognitive impairment in the elderly [100,101].…”

β-hexachlorocyclohexane as a Risk for Alzheimer’s Disease: A Pilot Study in North Indian Population

“…Inheritance of the ε4 allele of apolipoprotein E (APOE) is the strongest known genetic risk factor for AD. APOE is a polymorphic protein with 299 residues (Londono et al, 2012). The three common isoforms ApoE2, E3, and E4 differ by only two amino acid residues at positions 112 and 158 (Londono et al, 2012).…”

“…APOE is a polymorphic protein with 299 residues (Londono et al, 2012). The three common isoforms ApoE2, E3, and E4 differ by only two amino acid residues at positions 112 and 158 (Londono et al, 2012). There are two major functional domains, the N-terminal domain (NT) which contains the major receptor binding region and the Cterminal domain (CT) which contains the lipid binding region and is also thought to bind amyloid beta (Tamamizu-Kato et al, 2008;Liu et al, 2011).…”