Medical

New form of dementia discovered, redefining mainstream Alzheimer’s science

A newly defined neurodegenerative disease called LATE is characterized by entirely different protein aggregations in the brain than seen in Alzheimer's
A newly defined neurodegenerative disease called LATE is characterized by entirely different protein aggregations in the brain than seen in Alzheimer's
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A newly defined neurodegenerative disease called LATE is characterized by entirely different protein aggregations in the brain than seen in Alzheimer's
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A newly defined neurodegenerative disease called LATE is characterized by entirely different protein aggregations in the brain than seen in Alzheimer's

Dubbed by one scientist as, "probably the most important paper to be published in the field of dementia in the last five years," a team of researchers has described a newly defined neurodegenerative disease that closely mimics the symptoms of Alzheimer's, but which has an entirely different pathological cause.

Following a constant parade of failed clinical trials some researchers are reconsidering many of the basic foundations that underpin the mainstream consensus on Alzheimer's disease science. Toxic accumulations of amyloid and tau proteins have generally been considered the pathological hallmark of Alzheimer's disease and its related dementia but recently a variety of competing hypotheses have been raised.

This new study stemmed from the observation that while all patients with Alzheimer's may display some kind of dementia, not all patients displaying symptoms of dementia necessarily suffer from Alzheimer's.

"Recent research and clinical trials in Alzheimer's disease have taught us two things: First, not all of the people we thought had Alzheimer's have it; second, it is very important to understand the other contributors to dementia," explains Nina Silverberg, from the National Institute on Aging.

In a recently published report, the researchers describe a newly defined brain disorder called limbic-predominant age-related TDP-43 encephalopathy, or LATE. This disorder results in symptoms of dementia that significantly resemble Alzheimer's disease, however, the pathological signs in the brain are completely different.

"We proposed a new name to increase recognition and research for this common cause of dementia, the symptoms of which mimic Alzheimer's dementia but is not caused by plaques and tangles (the buildup of beta amyloid proteins that Alzheimer's produces)," says senior author on the new paper, Julie Schneider. "Rather, LATE dementia is caused by deposits of a protein called TDP-43 in the brain."

Prior research has indicated that when TDP-43 proteins become misfolded they can move from their normal location within a cell and aggregate in areas of the brain causing damage to an individual's memory or cognitive skills. It is suspected that abnormal TDP-43 pathology may be found in more than one in five people over the age of 80. And, it is this pathological source that could be causing the dementia often diagnosed as Alzheimer's in those subjects.

"…those of us who work in dementia have long been puzzled by our patients who have all the symptoms of Alzheimer's disease, but whose brains do not contain the pathological features of the condition," says University College London's Robert Howard, who did not work on this new study. "We have also been puzzled by a group of often very old patients whose dementia does not progress as rapidly as we would expect with Alzheimer's disease. We now know that these puzzling patients are probably suffering from LATE and not Alzheimer's disease and that LATE may be "mimicking" Alzheimer's in about 20 percent of cases."

Howard calls this new research, "probably the most important paper to be published in the field of dementia in the last five years," and says it should have major implications in how future drug trials for Alzheimer's disease are planned. Peter Nelson, corresponding author on the new research, agrees and suggests this broadening of our understanding into the causes of dementia will demolish the prior one-size-fits-all approach.

"LATE probably responds to different treatments than AD, which might help explain why so many past Alzheimer's drugs have failed in clinical trials," says Nelson. "Now that the scientific community is on the same page about LATE, further research into the 'how' and 'why' can help us develop disease-specific drugs that target the right patients."

The big challenge researchers now face is to rapidly develop specific, and sensitive, biomarkers that can identify patients suffering from LATE. This will not only improve Alzheimer's studies by removing these patients from clinical trials into drugs that potentially are not beneficial, but it will also allow for more granular study into this newly characterized disorder.

The implications of this new research are potentially quite profound. Bart De Strooper, from the UK Dementia Research Institute says this "excellent" study will cause many scientists to reevaluate the results from past failed clinical trials.

"The work will help to define in better ways the different forms of dementia and makes it necessary to have a second look at the failed amyloid trials: maybe part of the negative results are explained by the fact that we treated the wrong patients with the wrong drugs," De Strooper says.

The new report was published in the journal Brain.

Source: Rush University Medical Center, EurekAlert

5 comments
rederje
All is clearly associated to too much inflammation finishing in the brain. Eating junk food with remaining herbicides, Roundup, pesticides, antibiotics, hormones over the years increases inflammation, obesity, diabetes, heart and cardiovascular failures and demencia. Never eat junk too much transformed food, eat bio many natural fruits and vegetables and exercice quite more, over all your life, even old and you decreases your risk of dememntia by ten fold.
undrgrndgirl
they don't really know what causes alzheimer's so...
Bill Carpenter
I have found that using common natural plants and minerals helps with different aliments. For instance, Polk Weed which is high in vitamin A is a great body detoxing. Also Red Top Clover and Sassafras root is great for thinning and cleansing our blood. My question is why not do clinical trials using these natural cleansers? Would these not be useful in clearing our brains of excess buildup of toxins?
Tjoe
My 94 year old father is cognitively very much with it but has signs that I believe would be LATE related. Maybe that is where to look, in people that have active minds at 90+.
apprenticeearthwiz
The incidents of dementia may decrease when we no longer have bend our minds like pretzels trying to reconcile our evidence of how life on earth works with the artificial model created by our social operating systems. Some of the finest social operating systems money can buy.
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