The relevance of apolipoprotein E polymorphism to Alzheimer's disease
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The apo E gene located on chromosome 19 in humans is polymorphic. The three apo E isoforms E2, E3, and E4 are coded by three common alleles of the gene. The amyloid plaques in brains of Alzheimer disease (AD) patients are known to contain apo E. There is an increased prevalence of E4 allele in AD patients. apo E exhibits increased binding to a peptide Aβ deriving from amylold precursor protein. apo E, the risk factor for late AD disease is unable to prevent formation of paired helical filaments which in turn destabilizes neuronal microtubules.
A variety of molecular techniques are available for apo E genotyping using DNA amplified by the polymerase chain reaction (PCR). The high guanine to cytosine content of apo E is problematic to the extent that the yield of PCR product and hybridization stringency can be compromised. The specificity of diagnosis of late-onset AD can be improved when results of apo E genotyping are evaluated together with clinical criteria.