Previously it was believed that a mutation in the progranulin gene making the progranulin protein and supporting brain neurons is sufficient to produce a kind of dementia known as frontotemporal lobar degeneration (FTLD). An international team of experts from Mayo clinic have now laid hands on another genetic factor that probably protects against the disorder in progranulin mutation carriers. People with a mutated progranulin gene inheriting two copies of a specific variant of the TMEM106B gene appear significantly less likely to develop FTLD or have delay in disease onset.
At the time of the study, investigators utilized postmortem brain tissue for highlighting the apparent variation in the TMEM106B gene as a risk factor for FTLD. All the study subjects probably had lesions of misfolded TDP-43 proteins inside brain neurons. TMEM106B variants were supposedly involved in FTLD patients with a progranulin mutation who invariably have these brain lesions. In order to affirm that TMEM106B modulate progranulin levels, researchers analyzed TMEM106B variant in a new set of patients. While 82 FTLD patients registered progranulin mutations and 562 FTLD patients without mutations, 822 were as healthy controls. No considerable association with TMEM106B appeared, but a very significant link between TMEM106B variants and the development of FTLD in individuals with progranulin mutations was noted.
Individuals with a progranulin mutation also revealing two copies of the protective TMEM106B allele probably failed to develop FTLD or developed it at a much later age than is typical, which is normally around 60 years. Since progranulin mutation carriers produce 50 percent less progranulin protein, neuroscientist Rosa Rademakers, Ph.D. senior investigator, and colleagues assume that TMEM106B affects progranulin levels and therefore specifically works in people with progranulin mutations. It was ascertained that people carrying the protective TMEM106B allele have more progranulin in their blood plasma. Hence, TMEM106B allele possibly works for increasing progranulin protein levels. The protective form of TMEM106B may result in higher levels of progranulin in the blood.
The research was published in the December 22, 2010, issue of Neurology.