When is Alzheimer’s not Alzheimer’s? Researchers characterize a different form of dementia

LATE, a form of dementia that appears in the oldest-old is often mistaken for Alzheimer’s disease, but the brain pathology is very different. The protein TDP-43 appears to play a significant role in the development of LATE. The neurodegenerative disease may progress more gradually than A

In the past, using the terms Alzheimers disease and dementia interchangeably was common. Now there is a rising appreciation that a variety of diseases and disease processes contribute to dementia.

According to Nina Silverberg, Ph.D., director of the Alzheimers Disease Centers Program at National Institute on Aging (NIA), part of NIH, in the past many of the people who enrolled in clinical trials for Alzheimers drugs likely did not have amyloid the sticky substance that gums up neurons and interferes with thinking in their brains.

Recent research and clinical trials in Alzheimers disease have taught us two things: First, not all of the people we thought had Alzheimers have it; second, it is very important to understand the other contributors to dementia, she said.

For years, members of the scientific community have noticed that a large number of people who died in advanced age had symptoms of dementia without the telltale signs of amyloid or another common culprit, tau, in their brains at autopsy. Emerging research seemed to indicate that the protein TDP-43 contributed to that phenomenon.

More than 200 different viruses can cause the common cold, said Dr. Peter Nelson of the Sanders-Brown Center on Aging at the University of Kentucky, So why would we think there is just one cause of dementia?

A group of international researchers co-chaired by Nelson and Silverberg set out to define diagnostic criteria and other guidelines for advancing future research into this newly-named dementia, called LATE.

LATE, which tends to appear in the oldest-old, may seem the same as Alzheimers to the layperson, but the disease inside the brain looks very different. The incidence of LATE is almost as prevalent among the oldest-old as Alzheimers.

The groups work, published on April 30, 2019, in the journalBrain, established that like Alzheimers disease, LATE affects multiple areas of cognition, ultimately impairing activities of daily life, but it appears that LATE progresses more gradually than Alzheimers. However, LATE combined with Alzheimerswhich is a common combinationappears to cause a more rapid decline than either would alone.

For years, members of the scientific community have noticed that a large number of people who died in advanced age had symptoms of dementia without the telltale signs of amyloid or another common culprit, tau, in their brains at autopsy. Emerging research seemed to indicate that the protein TDP-43 contributed to that phenomenon. The image is in the public domain.

Nelson likens the committees work to Benjamin Franklins discovery of electricity.

People had seen lightning before of course, but Franklin helped formalize a concept that augmented our ability to study electricity, he said. By developing a sense of scientific focus around these data, we hope to jump-start a broad field of work to advance our understanding of this form of dementia and, ultimately, to open new opportunities for treatment.

Most importantly, Nelson added, its time to stop thinking of dementia as a one-size-fits-all disease.

LATE probably responds to different treatments than AD, which might help explain why so many past Alzheimers drugs have failed in clinical trials, he said. Now that the scientific community is on the same page about LATE, further research into the how and why can help us develop disease-specific drugs that target the right patients.

Funding:Funding included grants from NIH: U01AG016976, P01AG003949, R01AG03749, P50AG016574, R01AG054449, P30AG028303, P30AG012300, P30AG049638, P30AG010124, P30AG010161, P50AG047366, P50AG025688, P50AG005131, R37AG011378, R01AG041851, R01AG042210, R01AG017917, R01AG034374, UF1AG053983 and UF1AG057707.

Source: University of Kentucky

Original research:Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report . Peter T Nelson et al.Brain. doi:10.1093/brain/awz099


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