Shared protein pathology redefines treatment for multiple neurodegenerative diseases

On the surface, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE) might seem like unrelated diseases. ALS destroys motor neurons, causing muscle weakness and eventually paralysis. FTD hits the brain's frontal and temporal lobes, affecting language, personality and behavior. LATE is a slowly progressing memory disorder that resembles Alzheimer's disease and tends to affect people over 85.

But for all these distinctions, ALS, FTD and LATE share an important biological foundation, a protein called TDP-43. This commonality is generating an important question: Should we place greater emphasis on a disease's biological underpinnings than we do on its symptoms and other traits (phenotypes)?

To help answer this question, a large international group of clinicians, researchers and others, led by Michael Benatar, M.D., Ph.D., the Walter Bradley Chair in ALS Research and Executive Director of the ALS Center at the University of Miami Health System and the Miller School, have authored a paradigm-shifting review.

Published in JAMA Neurology on August, 24th, the paper titled "TDP-43-Associated Neurodegenerative Disease Conceptualization and Integrated Staging" dives into TDP-43's relationship with ALS, FTD, LATE and other severe neurodegenerative conditions, coining the term TDP-43 associated neurodegenerative disease (TAND) to describe these relationships. Viewing these diseases through a biological lens could profoundly impact biomarker research, clinical trials and eventually clinical care.