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More genes for Lou Gehrig's disease identified, according to Penn researchers
Date:4/7/2008

h either ALS or ALS combined with FTD and brains with pathological TDP-43 protein present and determined the DNA sequence of the gene for TDP-43 and compared it to the normal TDP-43 sequence in people without these diseases.

By doing this, we found two families in which a mutation was present and showed that the mutated gene tracked with the disease, says Van Deerlin. Within the same family, all people tested who have the disease carry the mutated form of TDP-43 and it was absent in the unaffected people tested.

With this, the research group then asked: Do we see this same change in people that dont have the disease outside of the families as controls? The group tested 747 Caucasian and 380 Chinese elderly people without the disease and didnt find the mutated form of TDP-43 in any of them.

What makes our paper completely distinctive is that we have post-mortem brain tissue from some individuals in one of the ALS families, says Schellenberg. We showed that people with a mutated form of TDP-43 actually have TDP-43 deposited in their brain.

The researchers stress the implications beyond ALS and FTD: TDP-43 shows up in a variety of diseases, for example 20 percent of Alzheimers cases. These findings are not just important to ALS, its every disease where there is a pathological form of TDP-43, notes Schellenberg. The next step will be to gain a better understanding of how the mutation in TDP-43 causes disease.


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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

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