Quantitative Assessment of Conformational Heterogeneity in Apolipoprotein E4 Using Hydrogen-Deuterium Exchange Mass Spectrometry.

Apolipoprotein E4 (apoE4) is the strongest genetic risk factor for Alzheimer's disease (AD). However, structural differences between apoE4 and the AD-neutral isoform, apoE3, still remain unclear. Recent studies suggest that apoE4 harbors intermediates. However, the biophysical properties and isoform specificity of these intermediates are not known. Here, we use the kinetics of hydrogen-deuterium exchange by mass spectrometry (HDX-MS) to examine the conformational heterogeneities in apoE3 and apo...