TDP-43 Pathology is Common in Old Age, and Correlates with Risk of Dementia
TDP-43 is the most recently discovered of the proteins known to be able to misfold or otherwise become altered in ways that encourage other molecules of the same protein to do the same. Like most of the other problem proteins, TDP-43 is involved in age-related neurodegeneration, and altered TPD-43 is commonly found in aged brains. As the study here makes clear, TDP-43 may be as important as the amyloid-β and tau of Alzheimer's disease. Finding ways to prevent pathological accumulation of the major varieties of altered proteins should be a priority for the research community.
A new type of degenerative brain disease, limbic-predominant age-related TDP-43 encephalopathy (LATE), was recognised just a decade or so ago, and remains relatively unknown. In the disease, the TDP-43 protein accumulates particularly in the limbic brain regions, which are also affected in the early stages of Alzheimer's disease. Accordingly, symptoms of LATE are similar to those of early Alzheimer's, but typically progress more slowly and are milder.
Researchers conducted the first study exploring the prevalence of LATE in a population-based Finnish autopsy dataset encompassing 300 Finns over the age of 85. LATE was found to be very common. Changes associated with the disease were identified in at least every second individual over the age of 85. The association between LATE and dementia was independent of other brain changes found in the study subjects. "The results suggest that LATE is, alongside Alzheimer's, one of the strongest determinants of dementia in the oldest old."