Here we outline the main findings from recent FTD center publications. Learn more about our research in easy to digest terms!

The following research summary is based on a recent 2018 publication (““UNC13A Polymorphism contributes to frontotemporal disease in sporadic amyotrophic lateral sclerosis”) from FTD Center graduate student, Katerina Placek. Great work, Katerina!

Common genetic variation influences neurodegeneration in amyotrophic lateral sclerosis

Background: What we already knew

  • Most (90-95%) patients with amyotrophic lateral sclerosis (ALS) do not have a known genetic, disease-causing mutation.
  • Half of all ALS patients develop symptoms of frontotemporal dementia (FTD).
  • Large, population-based studies have previously identified a commonly occurring variant of the UNC13A gene independently associated with both ALS and FTD.

Question: What we wanted to know

  • Is the genetic variation in UNC13A is related to the development of FTD in patients with ALS?

Findings: What this study shows

  • Placek and colleagues studied structural brain images and brain tissue samples in 190 patients with ALS.
  • Cortical thinning is a quantitative measure of brain cell integrity in the outer layers of the brain, and thinner cortex indicates greater cell loss. We found that patients with the disease-associated genotype in UNC13A had thinner cortex in frontal and temporal brain regions—the same regions that are thinner in patients with FTD.
  • Patients with the disease-associated genotype of UNC13A also had higher levels of TDP-43 – a protein found in the brains of patients with ALS and FTD – and worse performance on a cognitive skill called working memory. Working memory refers to the brain’s temporary storage of information that it is currently using and is essential for everyday tasks such as reasoning, decision-making, and planning. These skills commonly decline during the disease course of ALS and FTD.

Conclusions: What this study means

  • Symptoms of FTD in patients with ALS are associated with shorter survival times. The outcomes of this study may help physicians predict ALS patient prognosis and caregivers plan for the future.

Future Directions: What are the next steps

  • This research motivates future work evaluating genetic variation at UNC13A as a potential treatment target for ALS and FTD.

***To learn more, please visit:  https://www.sciencedirect.com/science/article/pii/S0197458018303567?dgcid=rss_sd_all

***This work made possible through the analysis of patient data from the Center for Neurodegenerative Research (CNDR) Brain Bank. For more information on participation in the Brain Bank program, please contact:

  • Kevin Davies at the Center for Neurodegenerative Disease Research by telephone at 215-662-4474 or by email at daviesk@upenn.edu 
  • Gabriela (Gabby) Bustamante, RN, BSN, at the Penn FTD Center by telephone at 215-662-3361
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