Alzheimer’s disease brings a lot of pain to people across the world. One has to sit and watch as their loved one almost literally fades away into a new person before death. It is hard to care for a family member who has this disease, but, with patience and perseverance, it can be done. More recently, experts in neurological disorders have recognized a disease that mimics the symptoms of Alzheimer’s disease but has different pathology. This disorder is called limbic-predominant age-related TDP-43 encephalopathy (LATE).
LATE is not a new condition; it has existed in the past, but experts have just recently recognized it. In fact, LATE was first reported on with clinical guidelines on the 30 of April this year. The goal of this is to hopefully encourage research into both this disease and Alzheimer’s while also allowing physicians to better distinguish cases that seem like Alzheimer’s but really are not. LATE, like Alzheimer’s, is another pathway that leads to dementia.
TDP-43 stands for transactive response DNA binding protein of 43 kDa. It is a protein that is commonly found to help regulate gene expression in the brain and other tissues. TDP-43, after being translated into a protein sequence, must undergo folding in the body so that it takes on the right shape. When it does not fold correctly, it can cause a plethora of problems like amyotrophic lateral sclerosis. Interestingly, misfolded TDP-43 has been found to be quite common in older adults.
The misfolded TDP-43 protein also contributes to shrinking of the hippocampus, an area of the brain involved with memory formation and storage. Through this mechanism, it is possible that TDP-43 leads to dementia. The hippocampal shrinkage linked to TDP-43 creates symptoms very similar to Alzheimer’s disease. Some experts believe that LATE’s impact on older people is nearly the same as or bigger than that of Alzheimer’s disease. Clearly, researchers believe that the TDP-43 protein is incredibly important.
This is where LATE and Alzheimer’s differ the greatest. In Alzheimer’s the culprit protein seems to be beta amyloid. Researchers do not know exactly what this protein does yet, but they do know that, when incorrectly cut, it can form aggregates in the brain. The aggregates, called amyloid plaques, are believed to cause inflammation and target brain cells for destruction. Researchers believe that this is a major contributor to dementia associated with Alzheimer’s disease.
Because LATE is so similar to Alzheimer’s disease, it has become a bit of a focus in new research. To create effective treatments for both disorders, scientists will need to know when a case is LATE versus when a case is Alzheimer’s. The differences between the pathology of the two diseases may even explain why clinical trials for Alzheimer’s treatments rarely provide effective medication. By disentangling and creating strict diagnostic criteria, this issue can be avoided.
LATE is sometimes mixed with Alzheimer’s disease to create a cocktail that leads to a quicker than usual degradation of memory and cognitive functioning. Despite this, LATE alone appears to work itself through the brain at a somewhat slower rate than Alzheimer’s does. Regardless, it is important to research and understand both of these diseases so that treatments can be made that lead to an improvement in people’s quality of life.
The new guidelines for LATE lay out three separate stages of the disease that should be evaluated for during autopsy. This first stage involves misfolded TDP-43 in the amygdala only, and the second involves the bad protein in the amygdala and the hippocampus. The final stage includes misfolded TDP-43 protein found in the amygdala, hippocampus, and middle frontal gyrus.
The guidelines also recommend a few other things. The first is that biomarkers need to be developed. Biomarkers are tests that allow one to know what is happening inside a living body, helping physicians treat accurately diagnose LATE before the autopsy. The recent publication also recommends that more pathology studies be done and that animal models be developed. Both of these would contribute to science’s understanding of the clinical picture of LATE.
Additionally, as new biomarkers become developed, the guidelines say that those with LATE should be removed from clinical trials for Alzheimer’s disease. These individuals may make a drug or treatment appear to be ineffective when it truly does work. This not only becomes a problem for science, but it also becomes a problem ethically. Although unknowingly, patients are being withheld from a treatment that could vastly improve life. Medicine owes it to these people to try again.
Commendations should be given to people who donate their body to science. Without the donor tissue, researchers would have a much harder time studying the pathology of disorders like LATE and Alzheimer’s. These donations can also help develop treatments and, maybe someday, cures for these diseases. Although the picture may appear bleak, scientists understand LATE better every day, and someday they will find out how to minimize the impact of this dementia-causing disorder.