LATE: A New Insanity

Between 15 and 20% of people diagnosed with Alzheimer’s actually have LATE dementia. It is a type of disorder that until now had been misdiagnosed as Alzheimer’s disease, since its clinical manifestations are similar.

It mainly affects the very elderly and causes a loss of memory and the ability to perform activities of daily living.

But how is this different from other related diseases?

What is LATE dementia?

The symptoms of LATE dementia are similar to those of Alzheimer’s disease. However, in this case the altered protein in the brain is TDP-43.

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

LATE is the acronym for TDP-43 encephalopathy , predominantly limbic age related. One of the differences with Alzheimer’s is that the altered protein in the brain is TDP-43, as suggested by this study by a team from Zhejiang University (China) . In the case of Alzheimer’s, it is the TAU and beta-amyloid proteins that are malfunctioning.

The TDP-43 protein is responsible for gene expression in the brain. A cluster of these “misfolded” proteins, that is, with a different shape than the original, is the cause of this disease.

The excess of these altered proteins produces neurotoxicity and neuronal degeneration. 25% of people over 85 years suffer enough alterations in this protein to present symptoms.

Who is affected by the disease?

Another difference that should be noted is that the probability of suffering from Alzheimer’s does not increase indefinitely with age. However, the risk of suffering from LATE dementia does, especially, from the age of 80.

The acronym LATE,  which in Spanish means ‘late’, was chosen because it also served to define this characteristic of the pathology. It is women who are at the highest risk of suffering from this disease, since today their life expectancy is greater than that of men.

Given that the number of people over 80 years of age will increase in a generalized way in the coming years, so will the incidence of this disease. LATE dementia can become a public health problem  in the following years.

How is LATE dementia diagnosed?

It has been in recent times, with the advancement of diagnostic techniques, when the TDP-43 protein has been more precisely identified. Currently, the most accurate methods 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 that we have already named. Another diagnostic technique is the search for accumulations of these proteins in the brain, with imaging techniques such as PET.

However, most of the time, the diagnosis of Alzheimer’s is based on the symptoms and the clinic. These biochemical tests that confirm the disease are rarely performed. This is why some of the misdiagnosed people actually have LATE dementia.

In the case of this type of disorder, the objective is to apply the same techniques as in the case of Alzheimer’s disease, but to search for the TDP-43 protein. The presence of a sufficient quantity of this protein in its altered form would confirm the diagnosis.

Symptoms of the disease

LATE disease produces symptoms that progress more slowly than in other types of dementias.  The stages are based on the affected brain area and increasingly affect:

• Stage 1: tonsil involvement. In this phase, in a subtle way, mood alterations begin to be perceived. Mood swings with agitation and even bouts of aggression 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 phase, it is the main reason why patients start to go to the doctor.
• Stage 3: involvement of the medial frontal gyrus. This manifests as behavioral and behavioral disturbances. Patients find it difficult to lead a normal life. It resembles a very advanced Alzheimer’s disease.

Research is the key

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

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

This will become increasingly important, since, as we have commented in previous sections, the incidence of this disease is expected to increase in the coming years.