New form of Alzheimer’s-like dementia identified

Written by Olivia Stevenson, Future Science Group

Researchers from Rush University Medical Center (IL, USA) along with several NIH-funded institutions, and in collaboration with international peers, have labeled a newly-defined cause of dementia. This pathway to dementia is known as limbic-predominant age-related TDP-43 encephalopathy (LATE).
Alzheimer’s disease (AD) is the most common form of dementia, and until now, the majority of dementia cases with memory loss have been labeled as AD. However, researchers are beginning to understand that numerous diseases can contribute to this. When the brains of individuals who have died with these conditions are examined, researchers are able to identify the different conditions.

In this study, published in Brain, researchers described a cause of dementia that has, until now, remained undefined. The symptoms of this cause of dementia and AD are strikingly similar, and it appears that some cases of dementia with memory loss may have been misdiagnosed as AD when really caused by LATE.

LATE dementia is caused by deposits of a protein known as TDP-43. When functioning normally, TDP-43 is associated with how cells utilize DNA to make proteins. However, in this disease, the protein becomes misfolded and moves from its typical location in the cell. Research has indicated that misfolded TDP-43 appears to particularly affect older adults. Enough misfolded TDP-43 to impact memory and cognition can be found in roughly 25% of individuals over 85 years-old.

The authors understand that the impact of LATE on public health is at least as great as that of AD, in individuals over the age of 80. Although LATE progresses more gradually than AD, when combined, there appears to be a quicker cognitive decline than in AD alone.

“We proposed a new name to increase recognition and research for this common cause of dementia, the symptoms of which mimic Alzheimer’s dementia but is not caused by plaques and tangles,” commented senior author, Julie Schneider (Rush Alzheimer’s Disease Center, IL, USA), “rather, LATE dementia is caused by deposits of a protein called TDP-43 in the brain.”

Further research is needed to gain a greater understanding of LATE. The researchers recommend generation of novel animal models to study the disease, as well as the development to aid in early diagnosis of individuals with the disease.

Importantly, the researchers also anticipate that by defining LATE, the development of AD drugs may be improved. By identifying and removing individuals with LATE from studies of AD drugs, the likelihood of breakthroughs in this area will increase.

“As we continue to make large strides in our understanding of memory loss and dementia in aging, we have renewed confidence that we will be able to work towards a more individualized approach to preventions and treatments,” concluded Schneider.