Human apolipoprotein E concentration in response to diseases and therapeutic treatments

Apolipoprotein (Apo) E is an important circulating and tissular protein involved in cholesterol homeostasis and many other functions. The common polymorphism in the coding region of the gene, four polymorphisms in the promoter region, other additional single nucleotide polymorphisms, as well as several ApoE variants have been identified. Outside genetic polymorphism effects, ApoE concentration is modulated in human plasma and tissue through many processes: 1) transcription regulation through hormone responsive elements; 2) cytokines; 3) compartmentalization in particles or linkage to HSPG; 4) degradation after oxidation, glycation, and proteolysis; and 5) through many specific and nonspecific receptor interactions. Is the level of ApoE in tissue or plasma critical in different pathologies such as cardiovascular diseases (CVD) or Alzheimer's disease (AD)? ApoE is able to bind to Abeta, tau, to be an antioxidant, to respond to inflammation, and is involved in cholesterol delivery, uptake, and accumulation. In experimental situations ApoE injection or positive modulation decreases cholesterol and triglycerides and improves cognitive impairment. ApoE peptides are involved in immune response. It seems more and more clear that low vs. high plasma concentration should be evaluated in large epidemiological studies. Only after such studies can the question be answered: Is a low or high concentration of ApoE beneficial or dangerous? This fascinating apolipoprotein will then be an interesting marker and/or drug target. (C) 2002 Wiley-Liss, Inc.