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Late onset Alzheimer's disease is characterized by the presence of plaques.  [[Amyloid beta]], a hydrophobic peptide, is a major component of these plaques '<ref>Lou, Jinghui et al.  2010.  In Silico Analysis of the Apolipoprotein E and the Amyloid β Peptide Interaction: Misfolding Induced by Frustration of the Salt Bridge Network.  PLOS.</ref>'.  ApoE has been observed to tightly bind with Aβ, an interaction that is hypothesized to influence the deposition of Aβ, thus contributing to the pathogenesis of LOAD '<ref>Chou, Chi-Yuan. et al.  2005. Structural Variation in Human Apolipoprotein E3 and E4: Secondary Structure, Tertiary Structure, and Size Distribution. Biophysical Journal 88:455–466.</ref>'.  A significant amount of Aβ is concentrated within the small paopulation of apoE-containing synapses; these two molecules have been observed to be highly colocalized in these synapses '<ref>Arold, S. et al.  2012.  Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer's disease and apoE TR mouse cortex.  Acta Neuropathol 123(1):39-52.</ref>'.  Concentrations of amyloid-β in the extracellular space of the brain are indicative of the balance between the synthesis and clearance of Aβ '<ref>Castellano, Joseph et al.  2011.  Human apoE Isoforms Differentially Regulate Brain Amyloid-β Peptide Clearance.  Sci Transl Med 3(89).</ref>'.  In fact, the Aβ concentration per synaptic terminal is notably lower in control subjects as compared to those exhibiting AD '<ref>Arold, S. et al.  2012.  Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer's disease and apoE TR mouse cortex.  Acta Neuropathol 123(1):39-52.</ref>'.  A deficit in clearance, rather than aberrant synthesis, is thought to be a factor in plaque formation '<ref>Arold, S. et al.  2012.  Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer's disease and apoE TR mouse cortex.  Acta Neuropathol 123(1):39-52.</ref>'.  ApoE4's ability to bind to Aβ is impaired, subsequently resulting in a reduced amount of receptor-mediated uptake and cellular metabolism of the apoE/Aβ complex.  Therefore, the E4 isoform of apoE is responsible for the reduced Aβ clearance that is characteristic of brains affected by AD '<ref>Chou, Chi-Yuan. et al.  2005. Structural Variation in Human Apolipoprotein E3 and E4: Secondary Structure, Tertiary Structure, and Size Distribution. Biophysical Journal 88:455–466.</ref>'.   

==Type III Hyperlipoproteinemia==   

Familial Type III hyperlipoproteinemia is a genetic lipid disorder that is marked by an increase in the concentrations of plasma cholesterol and triglyceride levels (Rall 82).  Normally, in individuals whose apoE is functional, chylomicron remnants and VLDL remnants are rapidly removed from circulation via recptor-mediated endocytosis within the liver.  However, this condition develops as a result of apoE that has impaired clearance abilities.  When a defect in apoE of this nature is present, delayed clearance in the plasma of triglyceride-rich lipoprotein remants results; significantly elevated levels of cholesterol-encriched remnant lipoproteins are a defining feature of this disorder '<ref>OMIM.Omim.org/entry/107741.</ref>' (Kashyap).  Individuals homozygous for the ε2 allele are most susceptible.  The E2 isoform of apoE exhibits weak or defective binding of remnants to hepatic lipoprotein receptors; the E2 isoform also clears these remnants from the plasma in a sluggish fashion '<ref>OMIM.Omim.org/entry/107741.</ref>'.  

=References=