Apo-E is a 34-36 kDa apo-lipoprotein synthesized largely by liver in
the body, and by astrocytes and microglia in the CNS.
ApoE forms a disulfide-linked complex: ApoE-AII-Amyloid Beta
which is roughly 50 kDaltons in size
It is found in
several alleles, E2, E3 and E4, with the latter known to increase the
risk of Alzheimer's disease pathology significantly.
Mice with ApoE 4 are found to have ten times the plaque load by age 15 months
that occur in wild type mice, whereas the absence of the ApoE gene in
knock-outs delay amyloid deposition, delay activation of glial cells,
and reduce the number of diffuse plaques according to Bales et al (2000).
According to Smith et al (1998), ApoE in human plasma occurs in
concentrations of 50-150 microgm/ml, but in brain at levels
of about 1 microgm/ml. According to Webster (Washington Neuroinflammation
Meeting, 2000) ApoE can inhibit fibrillogenesis of amyloid beta, with effects
at different concentrations as follows:
ApoE Concentration in nM
A-Beta Concentration for observed effect muM
400
80
2
250
ApoE binds to amyloid -Beta with the following binding kinetics
based on Yamaguchi et al (1999) [See link]: