Succinylation of Apolipoprotein E Drives Alzheimer’s Disease

Studies on the posttranslational modification of apoE have so far focused primarily on its glycosylation. Little is known about other PTMs that may confer disease risk in ε4 carriers. Our discovery that succinylation of apoE is increased in the 5xFAD hippocampus suggests that this modification occurs in response to disease pathology and opens the door to a new mechanism by which apoE function is regulated across the disease trajectory. We hypothesize that succinylation of apoE impacts functions critical for neuroprotection against AD in an allelic-dependent manner, and are currently investigating whether modulation of succinylation represents a novel therapeutic approach for AD.