ALS MND FTD FTLD C9orf72 prion spread TDP-43 TDP43


Follow the TDP-43 Road The spread of key proteins (red) between neurons in the brain and the spinal cord may in part explain the regional progression of the disease. Adapted from Braak, H. et al. (2013). Courtesy of Nature Publishing Group.

ALS occurs due to a progressive loss of motor neurons – the cells that enable muscles to move. One arm or leg may often be at first affected. But over time, the disease spreads throughout the body leading to paralysis and respiratory failure.

Researchers across the globe are working hard to understand how ALS spreads in hopes to develop more effective treatment strategies that stop the disease in its tracks. And, keep people with ALS moving.

One approach, led by University of Pennsylvania School Of Medicine’s John Trojanowski MD PhD, aims to retrace the ‘steps’ of ALS by tracking TDP-43, a protein that accumulates in motor neurons in more than 90% of people with the disease.

The strategy, pioneered by Universitätsklinikum Ulm neuroanatomist Heiko Braak MD in Germany, has provided insights into a growing number of neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease and most recently, frontotemporal dementia (FTD).

Now, the US-German team reports that ALS may travel through key regions of the brain using the axons that connect them. And, classifies the progression of the disease, based on the trajectory of TDP-43, into four distinct stages.

The results may enable clinicians in the future to predict the course of ALS in their patients.  And, inform their care.

ALS Today’s Michelle Pflumm PhD talked with University of Pennsylvania School of Medicine’s Virginia Lee PhD and John Trojanowski MD PhD about their latest findings and their potential implications for people with ALS going forward.


To find out about emerging methods to track ALS in people with the disease, check out our American Association for the Advancement of Science (AAAS) 2013 meeting report A Brave New World.


Brettschneider, J. et al. (2013) Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Annals of Neurology 74(1), 20-38.  Abstract  |  Full Text  

Braak, H., Brettschneider, J., Ludolph, A.C., Lee, V.M., Trojanowski, J.Q. and Del Tredici, K. (2013)  Amyotrophic lateral sclerosis-a model of corticofugal axonal spread. Nature Reviews Neurology 9(12), 708-714.  Abstract  |  Full Text   (Subscription Required) 

Further Reading

Ravits, J.M. and La Spada, A.R. (2009) ALS motor phenotype heterogeneity, focality and spread. Neurology 73(10), 805-811.  Abstract  |  Full Text