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I'm stuck on Genomics and these Polymorphisms predispose to Alzheimer’s Disease and coronary artery plaque formation.
> 1/9/2006 5:46:06 AM

So you can fairly ask what a Psychology Blog is doing worrying about the polymorphisms of Apolipoproteins which are the proteins that carry fats around in our blood stream. Well Gregor Mendel started all of this, so blame him not me. As a physician we were all forced to be fascinated by Genetics and the concepts of genotypes and phenotypes and wonder at the marvels of DNA, only now to be forced in our advancing age to rekindle all this learning to try and make it applicable to treating patients.
    Well Mendel was an Augustinian monk from 1865 living in Brno in the Czech Republic, who published his first work titled “Experiments in Plant Hybridization" in what I am sure many at the time would have thought as heretical if they only realized the importance of it. No one paid any attention to Mendel until 1900 and by then he was dead and his work with the common pea plant created the modern day scientific field of Genetics. So when we think of SNPs (Single Nucleotide Polymorphisms) and alleles tip your hat to that monk Gregor Mendel for pointing us in the right direction.
    Well back to Apolipoprotein E which comes in three main genetic alleles Apo E2, Apo E3 and Apo E4. The bad allele to be worried about is if you inherit from either or both of your parents a copy of the Apo E4 allele (you inherit one copy from each parent). So based on parental inheritance you have the possibility of being E2/E2, E3/E3, E4/E4 or E2/E3, E2E4 and E3/E4. If you inherit the Apolipoprotein E4 allele there has been strong association to both increased production of coronary artery plaque formation as well as early onset Alzheimer's Disease (AD). This polymorphism is more common that one might suspect and certainly carries with it the potential for developing two very debilitating diseases.
    A recent article in this month’s Archives of General Psychiatry underscores all this hoopla about the Apo E4 alleles. Apolipoprotein E Genotype and Age-Related Mylein Breakdown in Healthy Individuals by George Bartzokis M.D. et al. These authors discuss that “In addition to genotype-phenotype associations with vascular disease, the alleles and isoforms of Apo E4 have been related to dementias, most commonly Alzheimer’s disease. Apolipoprotein E (APOE) genotype is the most influentialAlzheimer disease (AD) risk factor after advanced age. The APOE4alleles decrease and the APOE2 alleles increase age at onsetof AD. Human and nonhuman primate data suggest that in midlife,the structural integrity of myelin sheaths begins breaking down,with an accelerating age-related trajectory most evident inthe brain's later-myelinating association regions. This mayresult in a progressive "disconnection" of widely distributedneural networks that may underlie the age risk factor for AD. The authors of this article conclude that in the later-myelinating regions of the brain, the severityand rate of myelin breakdown in healthy older individuals areassociated with APOE status and support the hypothesis thatthis process may contribute to age at onset of AD. CombiningAPOE status with noninvasive measures of myelin breakdown maybe useful in assessing treatment strategies for the primaryprevention of AD.”

    Well if you are brave enough to find out whether you possess this genetic variation of the Apo E4 allele it can be added to the list of other “risky genes” you may carry and want to be assayed for. Don’t expect your health insurance company to fork over for this lab charge.

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