Guidelines proposed for newly defined Alzheimer’s-like brain disorder

May 2, 2019

A recently recognized brain disorder that mimics clinical features of Alzheimer’s disease has for the first time been defined with recommended diagnostic criteria and other guidelines for advancing and catalyzing future research. Scientists from several NIH-funded institutions, in collaboration with international peers, described the newly-named pathway to dementia, Limbic-predominant Age-related TDP-43 Encephalopathy, or LATE, in a report published on April 30, 2019, in the journal Brain.

Alzheimer’s is the most common form of dementia, which is the loss of cognitive functions—thinking, remembering, and reasoning—and every-day behavioral abilities. In the past, Alzheimer’s and dementia were often considered to be the same. Now there is rising appreciation that a variety of diseases and disease processes contribute to dementia. Each of these diseases appear differently when a brain sample is examined at autopsy. However, it has been increasingly clear that in advanced age, a large number of people had symptoms of dementia without the telltale signs in their brain at autopsy. Emerging research seems to indicate that the protein TDP-43—though not a stand-alone explanation—contributes to that phenomenon.

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.

NIH has the full article