LATE

LATE – (LIMBIC-PREDOMINANT AGE-RELATED TDP-43 ENCEPHALOPATHY)

GENERAL ASPECTS

What is LATE?

LATE is the acronym used to refer to “limbic-predominant age-related TDP-43 encephalopathy”. It is a term that began to be used in 2019, to refer to the identification of deposits of the TDP-43 protein in a brain area called “limbic lobe”, especially in elderly subjects (over 80 years old).

What is TDP-43?

This is the acronym used to name the protein “Transactive response DNA binding protein of 43 kDa”. It is involved in the survival of nervous system cells. If it does not function properly, it can accumulate in deposits that are observed microscopically and promote neuronal degeneration.

How was LATE discovered?

In patients over 80 years of age whose most likely diagnosis during their lifetime was Alzheimer’s disease, when their brains were analyzed during autopsy it was found that, in addition to the characteristic Alzheimer’s lesions, a multitude of additional coexisting pathologies appeared that may contribute to cognitive impairment. In other words, it has been identified that, in many patients, not only beta-amyloid and tau (the proteins that define Alzheimer’s disease) are deposited, but there are also deposits of the TDP-43 protein (which define LATE), among others.

At what age does it appear?

It has been described mainly in the brains of elderly people (especially after 80 years of age), being more frequent at older ages. It has been found in up to 70% of people over 90 years of age.

What are the risk factors?

Age is the most relevant risk factor. Genetic risk factors have also been identified, which increase the probability of developing it. Some of these genes are common to Alzheimer’s disease and frontotemporal dementia (e.g. APOE or GRN).

What symptoms does LATE produce?

Brain deposition of TDP-43 contributes to the onset of cognitive impairment. The symptoms are indistinguishable from Alzheimer’s disease, because the same brain structures are usually affected as in Alzheimer’s disease. Moreover, since in most cases they appear together, it can be said that it acts by increasing the intensity of the symptoms that Alzheimer’s disease produces.

What is the evolution like?

When it appears in isolation, the course of symptoms is generally slower and more gradual than that observed in cases with Alzheimer’s disease. However, since, as we have said, it usually appears in combination, it has been observed to accelerate the speed of progression of symptoms with respect to those patients who only have Alzheimer’s lesions in their brain.

DIAGNOSIS

How can LATE be diagnosed?

The diagnosis of certainty can only be made post-mortem, through the analysis of the brain at the time of autopsy. During life, only a diagnosis of suspicion can be made, identifying symptoms similar to Alzheimer’s disease in elderly subjects, in whom the biomarkers used to detect Alzheimer’s disease are negative.

What complementary tests can be used?

Basically, a structural neuroimaging test (MRI or CT) will be performed, where atrophy will be observed mainly in the limbic region (hippocampus and nearby regions). This is a characteristic shared with Alzheimer’s disease, so it is often useful to use the tests used to diagnose it, such as, for example, biomarkers indicating beta-amyloid and tau deposition. If these are negative, the likelihood that the brain changes are caused by LATE increases.

TREATMENT

What drugs can be used?

Currently, as in other degenerative diseases, no therapy has been identified that is able to slow down or slow the progression of the disease. Since the symptoms are very similar to those of Alzheimer’s disease, it is possible that a slight improvement can be identified with them (e.g. with acetylcholinesterase inhibitors: donepezil, rivastigmine or galantamine).