LATE: Symptoms, Causes And Treatment Of This Dementia
If we talk about dementia, a large number of names may come to mind, but without a doubt there is one name that stands out among all the others: Alzheimer’s.
The deficits generated by this disease, highlighting the impairment it generates at the level of memory, and its typical evolution are generally well documented and known not only by the scientific community but also by the general population.
Now, 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 TDO-43 limbic-predominant age-related encephalopathy or LATE which we are going to talk about throughout this article.
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 a dementia highly similar to Alzheimer’s disease, in which alterations occur 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 die.
Although this dementia has been identified recently, the truth is that it is estimated that in fact around 20 to 50% of subjects over 80 years of age could suffer from it. It is more common in women, although it should 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 research on the matter identified it as a subtype of this. However, it is a different condition.
LATE dementia It is especially known for causing severe damage to the hippocampus, despite the fact that the first manifestations usually affect the limbic pathways. The dementia it generates is characterized by being affected at an amnestic 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 the condition worsens.
Progression in 3 phases
Although more research is needed, the studies carried out to date seem to indicate the existence of three major stages through which the disease evolves and generates increasing damage. In reality there are several proposed classifications, but in general the one taken by consensus that we have below is taken as a reference.
Phase 1: Tonsillar involvement
Unlike 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 cause alterations in mood and according to studies it causes a tendency towards agitation and even aggression in patients at this stage.
Phase 2: Affectation of the hippocampus
In a second phase, the hippocampus begins to be affected by encephalopathy. In this phase, memory is most compromised, and although it is not usually the first area affected, it is the alteration that is usually most recognized.
Gliosis and neuronal loss occur, in addition to the fact that sclerosis may appear comorbidly at the hippocampal level and an asymmetry may even be seen between both hemispheres. Astrocytosis and involvement of the entorhinal cortex can also be seen, with hypertrophied microglia. Additionally, the dentate gyrus, occipitotemporal, insula, and inferior olive also degenerate at this stage.
Phase 3: Affectation of the medial frontal gyrus
In this third stage, behavioral and behavioral alterations manifest, also causing severe impairment of daily living activities that can even be more severe than in other dementias. In addition to this region The frontal and temporal are also affected, something that leads to the appearance of symptoms similar to those of advanced Alzheimer’s. It is also common for subcortical degeneration to begin, especially at the level of the basal ganglia.
The causes of LATE, as with most other dementias, are not entirely known or understood. However, it has been observed that an aspect linked to its appearance is the presence in different points of the brain of TDP-43 protein accumulations
This protein is part of our body and is of great help when it comes to ensuring that the genes linked to the development and functioning of the brain are expressed correctly, but nevertheless When this protein is unfolded and in excess, it 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-related limbic-predominant TDP-43 encephalopathy there are no visible alterations of the TAU protein, something that abounds in Alzheimer’s in the form of the generation of neurofibrillary tangles that hinder synaptic transmission.
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 appearing increases as the years go by. Several analyzes have also been performed 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 symptomatology, dementia caused by encephalopathy known as LATE It is apparently very similar to Alzheimer’s, which is why until now it had not been identified as its own entity different from 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 a neurobiological level, as we mentioned in the previous section: while in Alzheimer’s, accumulations of TAU protein are observed in LATE, there are no major alterations in this protein, while there are in the TDP-43 protein (something which in turn is not common in Alzheimer’s).
Likewise, although in both pathologies brain regions such as the amygdala, hippocampus and middle frontal gyrus are affected, the order of presentation is different: in LATE the beginning of degeneration is seen at the level of the amygdala, while in Alzheimer’s it is the temporal lobe and the hippocampus which begins to degenerate.
But although they are different entities, it is also true that TDP-43 encephalopathy can appear associated with other disorders, which include Alzheimer’s (also amyotrophic lateral sclerosis and frontal dementias). In this sense, although the neurodegeneration caused by LATE It is much more gradual than in Alzheimer’s when it occurs on its own When both pathologies appear together, the neurodegeneration process is much faster than in either of the two conditions separately.
In search of a treatment
Currently there is no well-established treatment for this dementia, but the fact that it works differently from Alzheimer’s disease explains why many of the pharmacological treatments for what were believed to be cases of this disease do not exist. be successful.
Mechanisms and techniques must be explored to combat this disease, probably focusing attention on combating 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, more specific training and cognitive stimulation programs could be developed, although on the other hand the programs already developed are not specifically focused on Alzheimer’s but rather on the fight against the symptoms it generates, which in this sense are largely shared.
