LATE: symptoms, causes and treatment of this dementia

If we talk about dementias, a large number of names may come to mind, but without a doubt there is one name that stands out from all the others: Alzheimer's.

The deficits that this disease generates, highlighting the affectation that it generates at the memory level, and its typical evolution is something generally well documented and known not only by the scientific community but also by the general population.

However, Alzheimer's is not the only existing dementia, and we can also find some with similar symptoms and presentation styles. One of them, which in fact in the past was considered a subtype of Alzheimer's, has recently been considered an independent clinical entity: we are talking about limbic-predominant age-related TDO-43 encephalopathy or LATE, which we are going to talk about throughout this article.

• Related article: "Types of dementias: the 8 forms of loss of cognition"

Limbic-predominant age-related TDP-43 encephalopathy (LATE): what is it?

Limbic-predominant age-related TDP-43 encephalopathy or LATE is

a proteinopathy-type disease that generates dementia highly similar to Alzheimer's disease, in which there are alterations in the TDP-43 protein. It is a disease that generates neurodegeneration, and is characterized by causing a progressive loss of cognitive abilities as brain cells degenerate and dying.

Although this dementia has been recently identified, the truth is that it is estimated that done in about 20 to 50% of subjects over 80 years of age could suffer it. It is more frequent in women, although it must also be taken into account that life expectancy above eighty years of life is much lower in men. It has often been confused with Alzheimer's, and in fact although the first investigations in this regard identified it as a subtype of this. However, it is a different condition.

LATE dementia It is especially known for causing severe hippocampal involvement, despite the fact that the first manifestations usually affect the limbic pathways. The dementia that it generates is characterized by being affected at the amnesic level, and little by little as the disease progresses, other areas of the brain and other cognitive functions are affected.

The progression of this dementia is much slower than in other neurodegenerative pathologies, but it can be associated with others and in this case worsens the picture.

3 phase progression

Although more research is needed, the studies carried out so far seem to indicate the existence of three major stages through which the disease evolves and generates more and more affectation. Actually there are several proposed classifications, but generally the one taken by consensus that we have below is usually taken as a reference.

Phase 1: Tonsillar involvement

Contrary to what happens in other dementias, one of the first areas affected by dementia caused by LATE is the amygdala. initially being an affectation that occurs specifically in this brain region. This affectation can generate alterations at the level of mood, and according to studies there is a tendency to agitation and even aggressiveness in patients at this stage.

Phase 2: Involvement in the hippocampus

In a second phase, the hippocampus begins to be affected by encephalopathy. In this phase, memory is more compromised, and although it is not usually the first affected area, it is the alteration that is usually most recognized.

Gliosis and neuronal loss occursIn addition, it is possible that sclerosis may appear comorbidly at the hippocampal level and an asymmetry between both hemispheres can even be seen. Astrocytosis and involvement of the entorhinal cortex, with hypertrophied microglia, can also be seen. In addition, the dentate gyrus, occipitotemporal, insula and inferior olive also degenerate at this stage.

Phase 3: Medial frontal gyrus involvement

In this third stage, behavioral and behavioral alterations are manifested, also causing a severe impairment of activities of daily living that may even be more severe than in others dementias. Besides this region the frontal and temporal are also affected, something that leads to the appearance of symptoms similar to those of advanced Alzheimer's. Subcortical degeneration is also common, especially at the basal ganglia level.

Causes

The causes of LATE, as with most other dementias, are not fully known and understood. However, it has been observed as an aspect linked to its appearance is the presence in different parts of the brain of TDP-43 protein clumps.

This protein is part of our body and is of great help when the genes related to the development and functioning of the brain are expressed correctly, but nevertheless When splitting and in excess, this protein can be neurotoxic and generate neurodegeneration and the decrease in different cognitive abilities (including memory).

This factor also appears in other pathologies, but it is a quite relevant differential factor with respect to Alzheimer's disease. Furthermore, in age-predominant limbic-predominant TDP-43 encephalopathy, there are no visible protein alterations. TAU, something that abounds in Alzheimer's in the form of the generation of neurofibrillary tangles that hinder transmission synaptic.

Another risk factor, as its full name indicates, is age: This problem has been observed in people whose age ranged between seventy and eighty years of age, and its probability of appearance increases as the years go by. Several analyzes have also been carried out at the genetic level and the presence of mutations in genes such as GRN, APOE, and TMEM106B also seem to be risk factors.

Alzheimer's and LATE: two diagnoses that are easy to confuse

At the level of symptoms, dementia caused by encephalopathy known as LATE is apparently very similar to Alzheimer's, which is why until now it had not been identified as its own entity other than this one. In fact, the discovery of this pathology suggests that many of the cases diagnosed with Alzheimer's actually suffered from this recently discovered problem.

One of the main differences can be found at the neurobiological level, as we mentioned in the previous section: while in Alzheimer's they are observed accumulations of TAU protein in LATE there are no major alterations in this protein, while there are in the TDP-43 protein (something that in turn is not common in Alzheimer's).

Likewise, although both pathologies affect brain regions such as the amygdala, the hippocampus and the medial frontal gyrus, the order of presentation is different: in LATE the onset of degeneration It is seen at the level of the amygdala, while in Alzheimer's it is the temporal lobe and the hippocampus that begin to degenerate.

But although they are different entities, it is also true that TDP-43 encephalopathy may appear associated with other disorders that do include Alzheimer's (also amyotrophic lateral sclerosis and dementias frontal). In this sense, although the neurodegeneration caused by LATE it is much more gradual than in Alzheimer's when it occurs on its ownWhen both pathologies appear together, the neurodegeneration process is much faster than in either of the two conditions separately.

• You may be interested: "Alzheimer's: causes, symptoms, treatment and prevention

Looking for a treatment

There is currently no well-established treatment for this dementia, but the fact that it works differently from Alzheimer's disease makes it possible to explain why many of the pharmacological treatments for what were believed to be cases of this disease do not be successful.

Mechanisms and techniques to combat this disease should be explored, probably focusing attention on combating the excessive accumulation of TDP-43 protein. Likewise, once the existence of differences at the symptomatological level with Alzheimer's has been analyzed to a greater extent, they could develop more specific training and cognitive stimulation programs, although on the other hand programs already developed do not are specifically focused on Alzheimer's but on the fight against the symptoms it generates, which in this sense are largely shared.

Bibliographic references

• Nelson, P.T., Dickson, D.W., Trojanowski, J.Q., Jack, C.R., Boyle, P.A., Arfanakis, K., Rademakers, R., Alafuzoff, I., Attems, J., Brayne, C., Coyle-Gilchrist, I.T.S., Chui, H.C., Fardo, D.W., Flanagan, M.E., Halliday, G., Hokkanen, S.R.K., Hunter, S., Jicha, G.A., Katsumata, Y., Kawas, C.H., Keene, C.D., Kovacs, G.G., Kukull, W.A., Levey, A.I., Makkinejad, N., Montine, T.J., Murayama, S., Murray, M.E., Nag, S., Rissman, R.A., Seeley, W.W., Sperling, R.A., White III, C.L., Yu, L. & Schneider, J.A. (2019). Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain, awz99.