Happy New Year 2014!!!

Happy New Year 2014!!!

I wish all of you a Happy New Year 2014!!!

And take care when you go out tonight… :)

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What’s the problem with Apo E4 on a molecular level?

What’s the problem with Apo E4?:

The following image gives you an overview of the general tertiary structure of Apolipoprotein E3 as determined by x-ray cristallography (without binding any lipid components):

Apo E3 structure

(ADAPTED by [1])

The corkscrew-like parts of the protein are so called alpha-helices (a common secondary structure of proteins). In these, the amino acid sequence forms a helical configuration of the amino acid chain. There are two ends of the amino acid chain: the N-terminal end (ending with -NH2, on the left side) and the C-terminal end (ending with –COOH, on the right side). At position 112 – in the middle of the green helix – you find the Cysteine residue defining Apo E3. With Cysteine at position 112, the Arginine residue at position 61 (at the lower end of the blue helix) gets buried between alpha-helices. There is no relevant interaction between Arg61 and Glu255.

Now, let’s look at the same image for Apolipoprotein E4 – again this is derived from x-ray crystallography:

Apo E4 structure(ADAPTED by [1])

As you can see, in Apo E4 the Arginine residue at position 112 (in the green helix) forces the Arginine residue at position 61 (in the blue helix) to move outwards. This in turn facilitates a new, relative strong binding to the glutamate residue at position 255 (a so called salt bridge). As a consequence, you now have a domain interaction between the C-terminal and the N-terminal domain; both domains stick together very tightly. This domain interaction seems to be most relevant for the propensity to develop Alzheimer’s disease in patients who express Apo E4.

[1] Hatters, Danny M., Clare A. Peters-Libeu, and Karl H. Weisgraber. “Apolipoprotein E structure: insights into function.” Trends in biochemical sciences 31, no. 8 (2006): 445-454.

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New FAQ: How do I know my Apolipoprotein E genotype?

How do I determine my Apolipoprotein E genotype?

So how do I know what Apo E alleles I have?

There are basically two major approaches to determine which isoforms are found at your Apo E locus:

  1. The cheapest way nowadays is to order a kit from 23andMe (www.23andme.com) and perform SNP genotyping using the provided saliva-based DNA testing – they currently provide this service for 99 US$. SNP genotyping means that they do not sequence your entire genome but only look at certain positions where roughly 80 – 90 % most of the variation between individuals occurs. They can reliably determine the number of E4 alleles (i.e. 0, 1 or 2). They actually use a customized version of the HumanOmniExpress Bead Chip by Illumina. You might have read that 23andMe has recently run into problems with the FDA regarding the marketing and distribution of health-related DNA testing services. As a consequence, 23andMe stopped advertising with these features and they also will not provide the plain results. However, they will still provide the raw data as a raw-data file for download. You can use these raw data files and feed them into a SNP analysis tool (Promethease – https://promethease.com/ondemand) which will cost another 5 US$. This analysis will take around 10 – 20 minutes and will leave you with a clear result regarding the number of E4 alleles. The advantage of this approach is that you will have a dozen other genetic loci screened (e.g. traits for recessive disease such as cystic fibrosis).
  2. Most larger hospitals as well as many genetic counseling practices will nowadays be able to provide an analysis of the Apo E locus of your genome. These analyses are typically based on peripheral blood, from which lymphocytes are purified by centrifugation. DNA is then isolated from their nuclei and usually they use DNA probes based on hybridization to determine which isoform is located at the Apo E locus. This approach will give you results only for the Apo E locus. Prices vary between approx. 140 US$ and 250 US$ and will probably decrease in the future.
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Getting Started…

We have started to work on some FAQ’s. Check them out! Also, the wordpress version was changed to 3.8. I can’t wait to start reports on the latest research findings…

Happy holidays to all of you!!!!

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New Features on the Way…

Blog logo, some more features of wordpress and Apo_e4 twitter account created and uploaded…

Check back for continued updates; don’t forget to sign up for new blog posts!

How do you like the new logo?

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ApoE4 Blog in preparation


this site will soon be hosting a blog about Apo E4. Please keep checking back regularly – I need to figure a couple of tech things out before things can get going… you might have noticed that things have changed quite a bit here recently, I’m new to wordpress.

Kind regards!

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Apo E4 Blog


this website will soon be hosting a blog about the recent scientific findings regarding the allele Apolipoprotein E4.  (Apo E4).

Don’t forget to check back regularly…

With best wishes!


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