Apolipoprotein E (APOE) is a main apoprotein of the chylomicron that binds to a specific receptor on liver cells and peripheral cells. It functions in fat metabolism and is thought to be involved in the progression of Alzheimer’s disease and cardiovascular disease. It is an essential protein for the normal catabolism of triglyceride-rich lipoprotein constituents. Mutations in APOE result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants. APOE mutations are also implicated in atherosclerosis, multiple sclerosis, and impaired hippocampal development and cognitive function. In immunohistochemistry of normal tissue, APOE has cytoplasmic and plasma positivity in renal tubules, Leydig cells, hepatocytes, the adrenal gland, and in subsets of neurons throughout the brain. References: Neurology. 63 (10): 1898–901, PMID: 15557508; Science. 240 (4852): 622–30, PMID: 3283935; Science. 240 (4852): 622–30, PMID: 3283935; Science. 261 (5123): 921–23. doi:10.1126/science.8346443. PMID 8346443