Apolipoprotein E (
apoE), a 34 kDa circulating
glycoprotein of 299
amino acids, predominantly synthesised in the liver, associates with
triglyceride-rich
lipoproteins to mediate the clearance of their remnants after enzymatic lipolysis in the circulation. Its synthesis in macrophages initiates the formation of high density-like
lipoproteins to effect reverse
cholesterol transport to the liver. In the nervous system
apoE forms similar
lipoproteins which perform the function of distributing
lipids amongst cells.
ApoE accounts for much of the variation in plasma
lipoproteins by three common variants (
isoforms) that influence
low-density lipoprotein concentration and the risk of
atherosclerosis.
ApoE2 generally is most favourable and
apoE4 least favourable for cardiovascular and neurological health. The
apoE variants relate to different
amino acids at positions 112 and 158:
cysteine in both for
apoE2,
arginine at both sites for
apoE4, and respectively
cysteine and
arginine for
apoE3 that is viewed as the wild type. Paradoxically, under metabolic stress, homozygosity for
apoE2 may result in dysbetalipoproteinaemia in adults owing to impaired binding of remnant
lipoproteins to the
LDL receptor and related
proteins as well as heparan sulphate
proteoglycans. This highly atherogenic condition is also seen with other mutations in
apoE, but with autosomal dominant inheritance. Mutations in
apoE may also cause
lipoprotein glomerulopathy. In the central nervous system
apoE binds
amyloid β-
protein and
tau protein and fragments may incur cellular damage.
ApoE4 is a strong risk factor for the development of
Alzheimer's disease.
ApoE has several other physiological effects that may influence health and disease, including supply of
docosahexaenoic acid for the brain and modulating immune and inflammatory responses. Genotyping of
apoE may have application in disorders of
lipoprotein metabolism as well as glomerulopathy and may be relevant to personalised medicine in understanding cardiovascular risk, and the outcome of nutritional and therapeutic interventions. Quantitation of
apoE will probably not be clinically useful.
ApoE is also of interest as it may generate
peptides with biological function and could be employed in nanoparticles that may allow crossing of the blood-brain barrier. Therapeutic options may emerge from these newer insights.