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

• Published in: Electrophoresis Vol. 33; no. 24; pp. 3745 - 3755
• Main Authors: Londono, Carolina, DeKroon, Robert M., Mocanu, Mihaela, Booe, Jessica, Winnik, Witold M., Swank, Adam, Osorio, Cristina, Hamlett, Eric D., Alzate, Oscar
• Format: Journal Article
• Language: English
• Published: 01-12-2012
• Subjects: Hippocampus; Human; Lipids; Mice; Polyimide resins; Proteins; Risk; Solubility
• ISSN: 0173-0835; 1522-2683
• DOI: 10.1002/elps.201200219

Apolipoprotein
E
(
A
po
E
) is a major lipid carrier protein. In humans,
A
po
E
is expressed in three polymorphic isoforms, which are encoded by three different alleles
APOE
2,
APOE
3, and
APOE
4. In the brains of
A
lzheimer's disease (
AD
) patients, each one of these three allelic isoforms is found in several “isoelectric” protein isoforms (
q
PI
), i.e. protein isoforms resulting from
PTM
s 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
A
po
E
4; therefore, it is important to characterize the different
A
po
E
q
PI
s. 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‐
A
po
E
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.