LATE: A New Dementia

LATE dementia is a proteinopathy-like disease that causes clinical manifestations similar to those of Alzheimer’s disease. How does it develop? What are its characteristics ? In this article, we’ll tell you all about it.

Between 15 and 20% of people diagnosed with Alzheimer’s actually suffer from LATE dementia. It is a type of dementia that has so far been misdiagnosed as Alzheimer’s disease because its clinical manifestations are similar. Its incidence is expected to increase in the coming years.

This disorder mainly affects very old people. Like Alzheimer’s disease, LATE dementia causes loss of memory and the ability to perform activities of daily living. In this article we tell you what are the most important differences and features of this pathology.

What is LATE dementia?

LATE dementia is a proteinopathy-like disease, which means it is caused by the breakdown of certain proteins. It generates a dementia very similar in the clinic to Alzheimer’s disease.

LATE is the acronym for Age-Related Predominant Limbic Encephalopathy, TDP-43. One of the differences with Alzheimer’s disease is that the altered protein in the brain is TDP-43. In Alzheimer’s disease, it is the TAU and beta-amyloid proteins that are failing.

The TDP-43 protein is responsible for gene expression in the brain. A group of these “badly folded” proteins, that is, having a different shape from the original, is the cause of this disease.

The excess of altered proteins produces neurotoxicity and neuronal degeneration. A quarter of people over 85 have changes in this protein that are large enough to show symptoms.

Who is affected by this disease?

Another difference to note is that the likelihood of suffering from Alzheimer’s disease does not increase indefinitely with age. However, there is a risk of developing LATE dementia, especially after the age of 80.

The acronym LATE, which means “late” in English, was chosen because it also served to define this characteristic of the disease. Women are most at risk of suffering from it, as their life expectancy is now longer than that of men.

The number of people over the age of 80 will increase in the years to come, as will the incidence of this disease. LATE dementia could become a public health problem in the years to come.

How to diagnose LATE dementia?

It is recently, thanks to advances in diagnostic techniques, that the TDP-43 protein has been identified more precisely. Currently, the most accurate techniques for diagnosing Alzheimer’s disease are based on the study of biomarkers in cerebrospinal fluid.

These markers are the TAU protein and the beta-amyloid protein, which we have already mentioned. Another diagnostic technique is to look for accumulations of these proteins in the brain, using imaging techniques such as PET.

However, most of the time, the diagnosis of Alzheimer’s disease is based on symptoms and clinical observation. Rarely are these biochemical tests performed to confirm disease. This is why some people with Alzheimer’s disease actually have LATE dementia.

In the case of LATE dementia, the goal is to apply the same techniques as in the case of Alzheimer’s disease, but to look for the TDP-43 protein. The presence of a sufficient amount of this protein in its altered form would confirm the diagnosis.

Symptoms of the disease

LATE pathology produces symptoms that progress more slowly than in other types of dementia. Recent studies suggest that the disease progresses in three stages.

These stages are based on the affected area of ​​the brain and lead to more and more problems. These steps would be:

• Stage 1: tonsillar disorders. In this phase, we perceive subtle changes in mood. Mood swings with restlessness and even aggressive outbursts can occur
• Stage 2 : involvement of the hippocampus. When this area is affected, signs of memory loss begin to appear. Although this is not the first step, it is the main reason patients start seeing their doctor.
• Stage 3 : affection of the middle frontal gyrus. This manifests itself in changes in behavior and attitude. Patients find it difficult to lead normal lives. This stage looks like a very advanced stage of Alzheimer’s disease

Significance and conclusions

For now, the discovery of this new disease will not lead to changes in the diagnosis and treatment of the dementias known so far. However, it opened up new avenues of research.

Knowing more precisely the etiology of these diseases may lead to the development of specific treatments for each of them in the future.

Currently, there is no effective treatment for this type of pathology. This will become increasingly important, as, as we have commented in previous sections, the incidence of this disease is expected to increase in the years to come.