Mass Spectrometry Quantification Revealed Accumulation of C-terminal Fragment of Apolipoprotein E in the Alzheimer's Frontal Cortex*s

Published

April 11, 2013

Author(s)

Meiyao M. Wang, Illarion Turko

Abstract

Polymorphic variation in the apolipoprotein E (apoE) gene is the major genetic susceptibility factor for late onset Alzheimer's disease (AD) and likely contributes to neuropathology through various pathways. It is recognized that apoE undergoes proteolytic cleavage in the brain and that apoE fragments are likely having a variety of bioactive properties. ApoE fragmentation in the human brain was intensively studies using different immunochemical methods, but never been quantitative in its nature. Here we report absolute quantifications using multiple reaction monitoring mass spectrometry with 15N-labeled full-length apoE4 as internal standard. Measurements were performed on frontal cortex from control and severe AD donors. Our data points to predominant accumulation of C-terminal apoE fragment in the insoluble fraction of tissue homogenate for severe AD group versus control group. Further understanding of biological consequences of this accumulation might add to understanding of basic mechanism of AD pathology.

Citation

PLoS One

Volume

8

Issue

4

Pub Type

Journals

Download Paper

DOI Link

Keywords

multiple reaction monitoring, mass spectrometry, apoE, fragmentation, quantification, Alzheimer's disease

Citation

Wang, M. and Turko, I. (2013), Mass Spectrometry Quantification Revealed Accumulation of C-terminal Fragment of Apolipoprotein E in the Alzheimer’s Frontal Cortex*s, PLoS One, [online], https://doi.org/10.1371/journal.pone.0061498 (Accessed December 30, 2024)