The National Institutes of Health has announced the very first set of guidelines are now available for specific brain disorder that presents similarly to Alzheimer’s disease. The guidelines also feature diagnostic criteria and could be used towards conducting future research on the disorder, which scientists from various NIH research agencies have named Limbic-predominant Age-related TDP-43 Encephalopathy (LATE).
“While we’ve certainly been making advances in Alzheimer’s disease research — such as new biomarker and genetic discoveries—we are still at times asking, ‘When is Alzheimer’s disease not Alzheimer’s disease in older adults?’” said Richard J. Hodes, M.D., director of the National Institute on Aging (NIA) in the release. “The guidance provided in this report, including the definition of LATE, is a crucial step toward increasing awareness and advancing research for both this disease and Alzheimer’s as well.”
NIH says it’s become increasingly clear many people in their later years have symptoms of dementia without the telltale signs in their brain at autopsy. Emerging research seems to indicate that the protein TDP-43. I part, is a contributor.
TDP-43 (transactive response DNA binding protein of 43 kDa) is a protein that normally helps to regulate gene expression in the brain and other tissues. Prior studies found that unusually misfolded TDP-43 has a causative role in most cases of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. However, these are relatively uncommon diseases. A significant new development seen in recent research is that misfolded TDP-43 protein is very common in older adults. Roughly 25 percent of individuals over 85 years of age have enough misfolded TDP-43 protein to affect their memory and/or thinking abilities.
TDP-43 pathology is also commonly associated with hippocampal sclerosis, the severe shrinkage of the hippocampal region of the brain—the part of the brain that deals with learning and memory. Hippocampal sclerosis and its clinical symptoms of cognitive impairment can be very similar to the effects of Alzheimer’s.
“Recent research and clinical trials in Alzheimer’s disease have taught us two things: First, not all of the people we thought had Alzheimer’s have it; second, it is very important to understand the other contributors to dementia,” said Nina Silverberg, Ph.D., director of the Alzheimer's Disease Centers Program at NIA in the release.
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 importantly, 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. Additionally, 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.
LATE and TDP-43 also were featured as emerging scientific topics at the recent Alzheimer's Disease-Related Dementias Summit 2019, at which presenters foreshadowed research priorities covered in the Brain report.
