The overall goal of our study is to understand the effect of HNE modification on the structure and function of apolipoprotein E3 (apoE3) and apoE4, which play a critical role in brain cholesterol homeostasis. Immunoblots indicated HNE modification of recombinant apoE3 and apoE4 with a major band at ~36 kDa, while LC-MS/MS analysis revealed modification of H140 and H299 in both, and additionally at C112 in apoE3.