A recently recognized pathologic protein in the brain may play a larger role in the development of clinical Alzheimer’s disease dementia than previously recognized, according to a study by researchers at Rush University Medical Center. The findings of the study of nearly 1,000 older adults were published in the Sept. 30 issue of the journal Brain.
This combination, called “mixed pathologies,” increases the risk for developing diagnosed Alzheimer’s dementia above and beyond just having plaques and tangles in the brain.
“The clinical disease that we call ‘Alzheimer’s disease’ is looking more and more like the result of the accumulation of a number of disease processes in the brain of older persons,” James said. The majority of people with diagnosed Alzheimer’s dementia actually have mixed pathologies in their brains — not just the plaques and tangles that are the known hallmarks of Alzheimer’s disease.
“In particular, mixed Alzheimer’s and TDP-43 pathologies appear to be an under-recognized yet common form of mixed pathologies that contribute to the development of clinical Alzheimer’s dementia,” James said. “This is one of the first studies to examine TDP-43 and Alzheimer’s disease in the context of mixed pathologies.”
TDP-43 found in two-thirds of those with Alzheimer’s dementia
The Brain paper built on previous research by examining whether TDP-43 was associated with an increased likelihood of a diagnosis of Alzheimer’s dementia in people both with and without pathologic Alzheimer’s disease. The new study examined brain pathology, drawing on tissue samples from 946 deceased older men and women who had been enrolled in one of two cohort studies by the Rush Alzheimer’s Disease Center, the Rush Memory and Aging Project or the Religious Orders Study. Participants in both studies agree to donate their brains to research after their death.
TDP-43 was present in the brains of about half of the participants and in two-thirds of the brains of persons who had been diagnosed with Alzheimer’s dementia while alive. More than a third of the participants had mixed Alzheimer’s (plaques and tangles) and TDP-43 pathologies in their brain. Mixed Alzheimer’s and TDP-43 pathologies were associated with a higher likelihood of diagnosed Alzheimer’s dementia at death than plaques and tangles alone.
“These data are exciting because an improved understanding of the TDP-43 protein has potential to guide alternative treatment strategies for Alzheimer’s disease,” James said.