For 2 days in October 2018, in Atlanta, Georgia, a group of researchers gathered in a large conference room. There were 30 people – more if you counted those on speaker phone. The working group included international experts in brain imaging, clinical diagnosis, genetics, neuropathology, and neuropsychology, as well as the Director and other leaders of the National Institute on Aging’s Alzheimer’s Disease Research Centers Program. They were there to discuss a longstanding conundrum in Alzheimer’s research. It was time to acknowledge that the field has crossed a tipping point, beyond which it is no longer possible to study brain health, Alzheimer’s disease, or memory loss without paying attention to a protein called TDP-43.
TDP-43 protein (TAR DNA binding protein-43) is critically important for normal nervous system function, but it can undergo chemical changes and go rogue in the context of brain disease. It’s bad news for brain cells. Abnormal clumps of TDP-43 are the hallmark pathology of amyotrophic lateral sclerosis (ALS) and half of frontotemporal lobar degeneration (FTLD) cases. It also can appear in other neurodegenerative diseases, including Lewy body dementia, Huntington’s disease, and chronic traumatic encephalopathy.
