The Latest on LATE: A New Form of Dementia

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A scientist looking at brain scans on several computer screens.

Learn about a new form of dementia, called LATE. The article discusses how many people may have this form of dementia, the brain regions that are affected by this disorder, how it is currently diagnosed, and the next steps for research.

This is a summary of a more comprehensive article on LATE.

At the request of the National Institutes of Health, a group of neurodegenerative disease experts in topics ranging from neuropathology, psychiatry, gerontology, brain imaging and epidemiology (the study of how often diseases occur in different groups of people and why) met in late 2018 to consider better defining or re-conceptualizing a group of brain abnormalities and related symptoms that appeared to represent a previously poorly described (or understood) disease.

What is LATE?

The experts coined a new descriptive term, “Limbic-predominant Age-related TDP-43 Encephalopathy”, or LATE, to recognize and define this new disease and the major brain areas affected. They noted that the brain abnormalities are strongly associated with a dementia that can mimic Alzheimer’s disease (AD) or frontotemporal dementia (FTD).

LATE is different from other brain diseases associated with the TDP-43 protein, including forms of frontotemporal lobar degeneration, AD, and amyotrophic lateral sclerosis (ALS). This conclusion is based on where the TDP-43 protein is found in the brain, symptoms, and epidemiology.

How Many People May Have LATE?

Notably, in community-based observational studies, LATE is estimated to be present in up to 50 percent of older adults, usually referring to those over 70 - 80 years of age, with many not yet diagnosed with the symptoms of dementia.  LATE has an enormous, but largely unrecognized public health impact, among persons age 80 years of age and older.

How is LATE Diagnosed?

Currently, LATE can only be diagnosed exclusively by laboratory testing of the brain after death to establish the presence, abundance and distribution of the TDP-43 protein deposits. For these reasons, a working group was convened to develop diagnostic criteria for LATE, aiming to both stimulate research and to promote awareness of this pathway to dementia. 

What Brain Regions are Involved?

Although LATE appears to primarily affect the medial temporal lobe of the brain, imaging studies have demonstrated that individuals with LATE also have atrophy (the wasting away and death of cells) in the frontal lobes and other brain regions. 

Genetic Risk

Genetic studies have indicated that a number of genes appear to increase the risk for LATE. These discoveries suggest that LATE shares features of frontotemporal lobe dementia that that is associated with the TDP-43 protein as well as AD, but also that there may be other underlying mechanisms.

Next Steps

There remain many gaps in our understanding of LATE, including the absence of a diagnostic method, such as a blood test or brain imaging, for clinical detection of LATE.  Not only is more research needed to develop a diagnostic tool, but also to better define the disease’s risk factors and begin testing possible therapies in clinical trials.

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