Apolipoprotein genetic variants

Some people with elevated lipoprotein levels have VLDL that migrates on electrophoresis in the (3 band rather than the pre-(3 band (see Box 2-A). The presence of the (3-VLDL is associated with a high incidence of artery disease,218 which is most likely to develop in persons homozygous for a genetic variant of apolipoprotein E. The problem may arise because apo-E is required for receptor-mediated uptake of VLDL, which interacts both with tissue LDL receptors and with hepatic apo-E receptors. Genes for many of the... 

An apolipoprotein E variant is the only unequivocal genetic risk factor for late-onset Alzheimer s disease in a variety of ethnic groups. Caucasians and Japanese with the apo-E-s4 isoform have between 10 and 30 times the risk of developing Alzheimer s by 75 years of age. While the exact mechanism is unknown, evidence suggests an interaction with amyloid. Alzheimer s disease is characterised by plaques consisting of the peptide beta-amyloid. Apolipoprotein E enhances proteolytic breakdown of this peptide. However, the isoform apo-E-e4 is much less effective, which might result in an increased vulnerability to Alzheimer s in individuals with that gene variation. 

Mucke L, MasUah E, Johnson WB, Ruppe MD, Alford M, Rockenstein EM, Fotss-Petter S, Pietropaolo M, Mallory M, Abraham CR (1994) Synaptotrophic effects of human amyloid beta protein precursors in the cortex of transgenic mice. Brain Res 666 151-167 Nacmias B, Piccini C, Bagnoli S, Tedde A, Cellini E, Bracco L, Sorbi S (2004) Brain-derived neurotrophic factor, apolipoprotein E genetic variants and cognitive performance in Alzheimer s disease. Neurosci Lett 367 379-383... 

Modifications of the expression of plasma proteins can be related to genetic variations, complex combinations of post-translational modifications, alterations directly or indirectly related to diseases, or combinations of these mechanisms. Genetic variants of proteins such as haptoglobin, Gc-globulin, apolipoprotein E, apolipoprotein A-1, transferrin, or alpha-1-antitrypsin can be identified using 2-DE (Anderson and Anderson, 1979 Rosenblum et al, 1983 Tissot et al, 1993b Tissot et al, 2000b). 

The genetic basis for the more common late-onset AD appears more complex. Genetic susceptibility is more sporadic and it may be more dependent on environmental factors.9 The apolipoprotein E (apo E) gene on chromosome 19 has been identified as a strong risk factor for late-onset AD. There are three variants of apo E however, carriers of two or more of the apo E4 allele have an earlier onset of AD (approximately 6 years earlier) compared with non-carriers.9 Only 50% of AD patients have the apo E4 allele, thus indicating it is only a susceptibility marker. 

In 1993/1994 a series of publications caused a stir in the AD research community, since for the first time they linked a specific neuropathological process in late-onset AD to a genetic marker. Researchers looking at the composition of plaques found that the protein apolipoprotein E (ApoE) was associated with p-amyloid in the cerebrospinal fluid (CSF) of AD patients (Strittmatter et al., 1993). The gene for ApoE is on the same human chromosome (number 19) which was a risk factor in some AD pedigrees. The gene for ApoE comes in three versions (alleles) Apo s2, Apo s3 and, most importantly, Apo s4 these result in three slightly different variants of the protein. Humans carry two versions of the allele and so can have none, one or two of any of the versions of the Apo... 

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