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New insight into the cause of common dementia found by researchers at Mayo Clinic
Date:11/17/2010

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The protein made by the progranulin gene is found throughout the body, and performs different functions according to the type of tissue (organ) it is located in. But in the brain, it is believed to support neurons and keep them healthy.

Still, researchers do not really know how normal progranulin protein functions in the brain what other proteins it interacts with and so in this study they sought to uncover clues about progranulin biology by conducting a genome-wide association study (GWAS).

Based on their previous findings that a simple blood test is able to measure progranulin levels in plasma and could be used to identify patients with progranulin mutations, they tested blood from 518 healthy individuals in a GWAS to look for genetic variants that could explain some of the normal variability of progranulin levels in plasma. They found very strong association with two genetic variants in the same region of chromosome 1 and confirmed this finding in a second group of 495 healthy individuals.

By reviewing the scientific literature, they further ascertained that the same genetic variant found to be associated with plasma progranulin levels also affects the levels of the protein sortilin. Like progranulin, sortilin is found throughout the body and is involved in different tasks. In the brain, it is known to be important for survival of brain neurons.

"So, using a genetic approach, we identified a previously unknown connection between sortilin and progranulin," Dr. Rademakers says.

The researchers then studied the two proteins in cell culture and showed that the amount of sortilin in cells determines how much progranulin is taken inside or remains outside of a cell. "Our study shows that changes in the levels of sortilin result in different levels of progranulin available to cells. Given that we found FTLD patients often have less progranulin than they should, we believe that if you can manipulate levels of progra
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Contact: Kevin Punsky
punsky.kevin@mayo.edu
904-953-2299
Mayo Clinic
Source:Eurekalert

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