This review outlines the ways in which mass spectrometry-based methods have been used to paint a more complete picture of the most common neurodegenerative disorder, Alzheimer’s disease (AD), as it pertains to some of the most researched mechanisms of lipid involvement in the disease pathology: genetic predisposition involving the apolipoprotein E (APOE) Ɛ4 allele and APOE lipid processing, lipid peroxidation and associated oxidative stress, and inflammation. Here, APOE is linked to early-onset autosomal dominant Alzheimer disease.