**1. Introduction**

One player in health cognitive functioning is shown to be lipoproteins, essential in the metabolism and redistribution of lipids: cholesterol, phospholipids and triacylglycerol. There are several classes of lipoproteins which are used to transport lipids throughout the body and range in density (protein/lipid ratio); chylomicrons (contain dietary lipids), intermediate low density lipoproteins (IDL), very low density lipoproteins (VLDL, bad cholesterol), low density lipoproteins (LDLs) and the high density lipoproteins (HDLs, good cholesterol). The Apolipoprotein/Apoprotein gene family of proteins is part of the lipoprotein complexes that function as regulators of binding between lipoproteins and receptors. These proteins act as enzyme co-factors during lipid metabolism, helping to stabilize lipoproteins during transportation from cell or tissue to its destination [1].

Apolipoprotein E (ApoE), initially termed the "arginine-rich apoprotein", was first identified as a part of the VLDL complexes. ApoE is synthesized principally in the liver, but has also been found in other tissues such as the brain, ovaries, lungs, adrenals, spleen, muscle cells, and macrophages [2]. The three most common alleles of *ApoE* are *ApoE2*, *ApoE3*, *ApoE4* [3] found in the nervous system are primarily produced in astroglia and microglia. The three major isoforms differ at position 112 (*ApoE2*/*ApoE3* Cysteine, *ApoE4* Arginine) and 158 (*ApoE2* Cysteine, *ApoE3*/*ApoE4* Arginine), the amino acid substitutions at position 112 affect salt bridge formation within the protein, which ultimately impacts on lipoprotein preference, stability of the protein and on receptor binding activities of the isoforms [4]. Being an *ApoE4* carrier or having the *ApoE2/ApoE3* genotype is associated with

© 2012 Acevedo, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

higher triglyercide levels, higher VLDL levels, higher total cholesterol, higher total lipoproteins levels and elevated LDL or "bad cholesterol" levels all of which contribute to hypertension and diabetes confounding factors that have to be considered when designing a chemotherapy treatment regiment [5].

In rodent models, the lack of *ApoE* or ApoE4 protein expression leads to destabilization of cell membranes, increased apoptosis, and heightened sensitivity to neuronal trauma; whereas, ApoE3 and ApoE2 protein expression allow for healthy cell functioning and neuroprotection [4]. ApoE4 has detrimental effects in transgenic mice, including behavioral abnormalities, such as deficits in spatial learning and memory using Morris water maze (MWM) [6], as well as significant alterations in the hippocampus and cortex [4,7]. The studies in mice are consistent with clinical studies indicating reduced spatial learning and memory in those who carry the *ApoE4* allele [8]. Experiments have also demonstrated that the three isoforms of human *ApoE* gene have different effects on the development of neurodegenerative diseases. Those individuals that are *ApoE4* carriers have an increased risk of age-related mild cognitive impairments (MCI) and the development of Alzheimer's disease (AD) particularly in females [9].

In ovarian cancer, ApoE protein levels act as a potential tumor-associated marker as found in serous carcinomas, but not in serious borderline or normal ovarian surface epithelium cells [10]. Up-regulation of ApoE protein levels is also seen in breast carcinomas, pancreatic cancer, stomach carcinomas, colon carcinomas and prostate carcinomas [10]. Blockage of ApoE expression in the serous carcinoma cell lines leads to cell cycle arrest and apoptosis. Women infused with ApoE protein at the time of diagnosis showed significantly higher survival rates [10]. This data suggest that upregulation of ApoE expression may be a defense mechanism to help body fight carcinomas.
