Researchers define LATE — an Alzheimer’s-like brain disorder

photoLimbic-predominant Age-related TDP-43 Encephalopathy, or LATE, as seen by microscope and MRI. Nelson et. al. and Brain.

A brain disorder that mimics symptoms of Alzheimer’s disease has been defined with recommended diagnostic criteria and guidelines for advancing future research. The disorder is being called LATE — short for Limbic-predominant Age-related TDP-43 Encephalopathy. Those at greatest risk of contracting it are the so-called “oldest-old.”

Researchers at Rush University Medical Center in Chicago and scientists from several National Institutes of Health-funded institutions described the newly-named pathway to dementia in a report published today in the journal Brain.

“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 (the buildup of beta amyloid proteins that Alzheimer’s produces). Rather, LATE dementia is caused by deposits of a protein called TDP-43 in the brain,” said Dr. Julie Schneider, senior author of the Brain paper and associate director of the Rush Alzheimer’s Disease Center.

Alzheimer’s, the most common form of dementia, causes loss of cognitive functions — especially memory — but also results in changes in everyday functional abilities and behavior. In the past, most cases of dementia with memory loss were assumed to be Alzheimer’s disease.

Now there is growing appreciation that a variety of diseases and disease processes contribute to dementia with memory loss. Each of these diseases appears differently in brain samples examined at autopsy of people who died with these conditions.

‘Oldest old’ are at greatest risk of LATE

It has become increasingly clear that in advanced age, a large number of people had symptoms of dementia without the telltale signs of Alzheimer’s disease in their brains at autopsy. Emerging research seems to indicate that TDP-43, while not a stand-alone explanation, is a large contributor to that phenomenon.

In the disease, TDP protein becomes misfolded (abnormally structured) and moves from its normal location in the cell. Recent research shows that misfolded TDP-43 protein is very common in older adults. Roughly 25 percent of individuals more than 85 years of age have enough misfolded TDP-43 protein to affect their memory and/or thinking abilities.

The authors wrote that LATE is an under-recognized condition with a very large impact on public health. They emphasized that the “oldest-old” are at greatest risk, and they believe that the public health impact of LATE is at least as large as Alzheimer’s in this group.

The clinical and neurocognitive features of LATE affect multiple areas of cognition, ultimately impairing activities of daily life. Based on existing research, the authors suggested that LATE progresses more gradually than Alzheimer’s. However, LATE combined with Alzheimer’s — which is common for these two highly prevalent brain diseases — appears to cause a more rapid decline than either would alone.