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LATE: A Disease That Mimicks Alzheimer’s Disease


A recent article, published in the Oxford journal Brain, categorizes and draws attention to an age-related disease that impacts the brain yet is widely unknown, even among scientists: limbic-predominant age-related TDP-43 encephalopathy (LATE) [1].

The symptoms of this disease are similar to those of Alzheimer’s disease. It causes cognitive impairment and, when presenting alongside Alzheimer’s disease, can lead to even faster degeneration along with heightened agitation and aggression.

This new disease has been found to impact very specific areas of the brain – generally traveling vertically through the brain, it degenerates areas partly responsible for emotions, memory, and language, influencing different areas depending on its stage.

LATE, much like Alzheimer’s disease, is thought to be caused in some part by a misfolded protein. While Alzheimer’s may be caused by the accumulation of the proteins amyloid beta and tau [2], LATE may be caused by the accumulation of a modified version of the TDP-43 protein outside of its normal area in the cell (the nucleus). This can be detected after the death of a patient by staining the modified protein, thus allowing us to differentiate it from Alzheimer’s, but no methods to detect this in living people have yet been tested. Still, it has been suggested that the two diseases could be told apart by looking at the level of degeneration in the brain; this suggestion has, so far, not been put to use.

Who does LATE affect?

LATE is thought to affect between 20-50% of the population over 80 years of age and is much more strongly associated with aging than Alzheimer’s disease is – given the expected increase in average lifespan over the next few decades, the burden that LATE has on the overall population in terms of disease and healthcare spending is expected to rise. Already, some scientists suggest that somewhere between 15-20% of diagnosed elderly Alzheimer’s sufferers may instead be suffering from LATE [1], and this proportion is higher in even older patients.

LATE appears to accelerate the deterioration of the brain in sufferers of Alzheimer’s disease, causing greater degeneration than either disease would have caused alone. It should be noted that sufferers of LATE often also have Alzheimer’s disease or, at least, suffer from similar diseases [1].

It is also likely that LATE has had a negative impact in the development of a cure for Alzheimer’s disease, as trials of Alzheimer’s treatments may have unknowingly accepted patients who suffer from both diseases. A treatment that cured Alzheimer’s would be unlikely to treat LATE as well, meaning that the degeneration caused by LATE could mask the beneficial impact of the treatment and prevent a genuine Alzheimer’s cure from passing clinical trials and being released to the market. Therefore, future trials aimed at treating Alzheimer’s disease must attempt to account for this influence.

What causes LATE?

The protein TDP-43, after modification by small molecular groups called phosphates, is suspected to be the primary cause of LATE. This modified version of TDP-43 is able to leave the cell’s nucleus and start causing damage in areas where it is not meant to be, though it is not known how exactly it causes this; the available evidence only states that this modified version of TDP-43 is loose in the brain cells of sufferers of LATE, while the normal protein that should be in the nucleus is missing [1].

Interestingly, this modified TDP-43 is thought to cause another disease, ALS [3] – the degenerative disease from which Stephen Hawking suffered and the disease that the popular Ice Bucket Challenge was attempting to raise awareness of. This raises the question of whether or not the two diseases share any common causes. Sadly, ALS remains uncured, and the question of its causes remains controversial, with its main therapy focused on delaying its progression by turning off a certain signaling system.

With both ALS and LATE having significant uncertainty surrounding their causes, a lot more research will be needed to measure the impact of TDP-43 and to begin work on therapies to treat these diseases.


Sadly, not much is known about how TDP-43 causes LATE, how to detect LATE in living people and differentiate it from Alzheimer’s disease, or how to treat it outside of suggestions and hypotheses. More experimentation is needed before we can answer any of those questions with certainty. The next steps are to differentiate LATE from Alzheimer’s by the degree of degeneration in the brain and develop therapeutics to break down this damaged TDP-43.

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[1] Nelson, P. T., Dickson, D. W., Trojanowski, J. Q., Jack, C. R., Boyle, P. A., Arfanakis, K., … & Coyle-Gilchrist, I. T. (2019). Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain.

[2] Bloom, G. S. (2014). Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA neurology, 71(4), 505-508.

[3] Mackenzie, I. R., & Rademakers, R. (2008). The role of TDP-43 in amyotrophic lateral sclerosis and frontotemporal dementia. Current opinion in neurology, 21(6), 693.

About the author
Patrick Deane

Patrick Deane

As an undergraduate of Human Biosciences at Plymouth University, aging research has been Patrick’s passion for a long time now. While he has aspirations to later directly join the research effort, for now, he provides the community with educational articles, spreading knowledge of the biology behind the aging process while he himself learns.
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