If we’re talking about dementia, it’s possible that a lot of names come to mind, but there is definitely one name that stands out from all the rest: Alzheimer’s disease.
The deficits generated by this disease, highlighting the impact it generates at the level of memory, and its typical evolution is something generally well documented and known not only by the scientific community but also by the population in general.
However, Alzheimer’s disease is not the only dementia that exists, and we can also find it with similar symptoms and styles of presentation. One of them, which was actually considered an Alzheimer’s subtype in the past, was recently considered an independent clinical entity: we are talking about age-related TDO-43 predominant limbic encephalopathy or TARD, Which we will talk about throughout this article.
Age-related TDP-43 Predominantly Limbic Encephalopathy (TARD): What is it?
Age-related TDP-43 limbic encephalopathy or TARD is a proteinopathy-like disease that causes dementia very similar to Alzheimer’s disease, In which alterations in the TDP-43 protein occur. It is a disease that generates neurodegeneration and is characterized by a progressive loss of cognitive abilities as brain cells degenerate and die.
Although this dementia has recently been identified, the truth is that it is estimated that in fact between 20 and 50% of people over the age of 80 may suffer from it. It is more common in women, although it should also be borne in mind that life expectancy above eighty years is much lower in men. It has often been confused with Alzheimer’s disease, and even early research in this regard identified it as a subtype of it. However, this is a different condition.
Dementia by LATE it is particularly known to cause severe hippocampal damage, Although the first manifestations usually affect the limbic pathways. The dementia it generates is characterized by amnesic involvement, and 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 picture worsens.
Progression in 3 phases
Although more research is needed, studies to date suggest that there are three major stages through which the disease progresses and generates increasing involvement. There are actually several proposed classifications, but in general, the consensus below is usually taken as a reference.
Phase 1: involvement of the tonsils
Unlike what happens in other dementias, one of the first areas affected by dementia caused by TARD is the amygdala. initially being an affectation that occurs specifically in this region of the brain. this assignment it can cause mood swings, And according to studies causes a tendency to restlessness and even aggression in patients at this stage.
Phase 2: Involvement of the hippocampus
In a second phase, the hippocampus begins to be affected by encephalopathy. At this point, memory is more compromised, and while this is usually not the first area affected, it is the impairment that is usually recognized the most.
Gliosis and neuronal loss occurIn addition, it is possible that the sclerosis occurs comorbidly in the hippocampus and an asymmetry between the two hemispheres can even be observed. Astrocytosis and involvement of the entorhinal cortex, with enlarged microglia, may also be observed. In addition, the dentate gyrus, occipitotemporal, insula, and lower olive also degenerate at this stage.
Phase 3: Deterioration of medial frontal rotation
In this third stage, behavioral and behavioral alterations manifest themselves, also causing a serious alteration in the activities of daily living which may even be more severe than in other dementias. In addition to this region the frontal and temporal are also affected, Which leads to the appearance of symptoms similar to those of advanced Alzheimer’s disease. It is also common for subcortical degeneration to begin, especially in the basal ganglia.
The causes of TARD, like most other dementias, are not fully known and understood. However, it has been observed that an aspect related to its appearance is the presence at different points of the brain of TDP-43 protein accumulations.
This protein is part of our body and is very useful when genes related to the development and functioning of the brain are properly expressed, but nonetheless when unfolded and in excess, this protein can be neurotoxic and generate neurodegeneration and the decrease in various cognitive skills (including memory).
This factor also appears in other pathologies, but it is a very important differentiating factor vis-à-vis Alzheimer’s disease. In addition, in age-related limbic TDP-43 encephalopathy, there are no visible alterations in the TAU protein, which in Alzheimer’s disease abounds in the form of the generation of tangles. neurofibrillaries that interfere with synaptic transmission.
Another risk factor, as the full name suggests, is age: This problem has been observed in people ranging in age from seventy to eighty, and the likelihood of it occurring increases over time. Several genetic analyzes have also been performed and the presence of mutations in genes such as GRN, APOE and TMEM106B also appear to be risk factors.
Alzheimer’s and LATE: two diagnoses that are easy to confuse
In terms of symptoms, dementia caused by so-called TARD encephalopathy it is apparently very similar to Alzheimer’sTherefore, until now, it had not been identified as its own entity other than this. In fact, the discovery of this pathology suggests that many cases diagnosed with Alzheimer’s disease have in fact suffered from this recently problematic finding.
One of the main differences can be found at the neurobiological level, as we discussed in the previous section: while in Alzheimer’s disease there are accumulations of TAU protein in LATE, there is no major alterations in this protein, while in the TDP-43 protein (something not common in Alzheimer’s disease).
Also, although in both pathologies the cerebral regions such as the amygdala, the hippocampus and the middle frontal gyrus are affected, the order of presentation is different: in LATE, the onset of degeneration is observed at the level of the amygdala, while in Alzheimer’s disease it is the temporal lobe and the hippocampus that begin to degenerate.
But even though they are different entities, it is also true that TDP-43 encephalopathy can be associated with other disorders including Alzheimer’s disease (also amyotrophic lateral sclerosis and frontal dementias). In this regard, although the neurodegeneration caused by LATE it is much more progressive than in Alzheimer’s disease when it occurs aloneWhen the two pathologies appear together, the process of neurodegeneration is much faster than under either of the two conditions separately.
In search of treatment
There is currently no well-established treatment for this dementia, but the fact that it works differently from what Alzheimer’s disease would do helps explain why many pharmacological treatments “this disease will not work” for.
Mechanisms and techniques must be explored to combat this disease, Probably focusing on combating excessive accumulation of TDP-43 proteins. Also, once the existence of symptomatic differences with Alzheimer’s disease has been analyzed to a greater extent, they could develop more specific training and cognitive stimulation programs, although on the other hand the programs already developed are not specifically targeted. the fight against the symptoms it generates, which in this sense are widely shared.
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