[ad_1]
Allan Gallup, a lawyer and retired businessman, has lost his memory more and more in his later years. Finally, he could not remember how to use a computer or television. Although he needed a catheter, he did not stop forgetting and taking it out.
It was Alzheimer's disease, the doctors said. So after Gallup's death in 2017 at the age of 87, his brain was sent to the University of Washington. in St. Louis to be considered as part of a national study of the disease.
But the researchers discovered that it was not just about Alzheimer's disease. Although Gallup's brain has all the distinguishing characteristics (plates consisting of an abnormal protein and entangled chains of another), the tissue also contained protein clusters called Lewy bodies, as well as signs of accidents. cerebral vascular Each of these, too, is a cause of dementia.
Mr. Gallup's brain was typical of an elderly patient with dementia. Although almost all of these patients are diagnosed with Alzheimer's disease, they almost all have a mixture of brain abnormalities.
[[[[Like the Science Times page on Facebook. | Sign up for the Science Times Bulletin.]
For researchers trying to find treatments, these so-called mixed pathologies have become a huge scientific problem. Researchers can not say which of these conditions is the cause of memory loss in a particular patient, or whether all together are to blame.
Roderick A. Corriveau, who leads the dementia research programs at the National Institute of Neurological Disorders and Stroke, says that these abnormalities are themselves the effects of a cause of dementia yet to be discovered.
These questions are about the very definition of Alzheimer's disease. And if you can not define the condition, how can you find a cure?
In addition to plaques and tangles, other nasty potentials found in the brains of people diagnosed with Alzheimer's disease include silent strokes and other diseases of the blood vessels, as well as a poorly understood disease called sclerosis. hippocampus.
Potential culprits also include an accumulation of Alpha-synuclein, the abnormal protein that makes up Lewy bodies. And some patients still have another abnormal protein in their brain, TDP-43.
Nobody knows how to address the multitude of other potential problems encountered in the brains of patients with Alzheimer's disease. So until recently, they were mostly ignored.
"I would not say it's a dirty little secret," said Dr. John Hardy, a researcher on Alzheimer's at University College London. "Everyone knows it. But we do not know what to do about it. "
During the interviews, some experts said that they had hesitated to speak a lot of mixed pathologies, for fear of appearing too negative. But "at some point, we need to be a little more realistic and rethink what we are doing," said Dr. Albert Hofman, chairman of the T.H. Epidemiology Department at Harvard. Chan School of Public Health.
The problem has begun with the very discovery of Alzheimer's disease. In 1906, Dr. Alois Alzheimer, German psychiatrist and neuroanatomist, describes a 50-year-old woman with dementia.
At autopsy, he discovered special plaques and twisted proteins resembling spaghetti, known as entanglements in his brain. Since then, they have been considered as the defining features of Alzheimer's disease.
But scientists now think that this woman must have had a very rare genetic mutation guaranteeing that a person will have a pure form of Alzheimer's in middle age.
Patients with the mutation appeared to develop only plaques and tangles, and no other pathology. For decades, plaques and entanglements have been at the center of dementia research.
The rare genetic mutations have led to an overproduction of amyloid, the abnormal protein in these plaques. According to many scientists, amyloid was the root cause of Alzheimer's disease.
More plaques usually meant more severe dementia, in older and younger patients. The researchers therefore tested drugs that could attack amyloid or stop its production in genetically modified mice. The drugs worked perfectly.
Scientists have recognized that mice are an imperfect model – they never develop dementia – but the studies were encouraging. So it was a huge disappointment that these drugs failed again and again in clinical trials on patients.
Anti-plaque drug testing continues despite growing recognition that many factors may be associated with dementia – or perhaps the real cause remains to be discovered.
"What motivates us is the depth of unmet need," he said. Dr.. Dan Skovronsky, scientific director of the pharmaceutical company Eli Lilly, who continues his research on anti-amyloid treatments.
"That's why we keep moving forward. But it's such a difficult problem, and it's made more difficult because of the mixed pathology. "
What to do now? Scientists are struggling to reframe the problem. Some think research should be more age-centric.
"We can not avoid the fact that the number one risk factor for Alzheimer's is age, and many of these other conditions are associated with age," said Dr. John Morris, a professor of neurology at Washington University.n St. Louis. "We do not see them in young people."
Carol Brayne, an epidemiologist at the University of Cambridge, has been saying this for decades. She found something important about the obvious fact that the The older a person gets, the more likely they are to develop dementia. At 90, one in two people has dementia.
A more optimistic view is that there may be something in the brain that triggers a cascade of multiple pathologies. If this is true, blocking this factor could stop the process and prevent dementia.
Dr. Hofman is convinced that the triggering factor is the decrease of blood flow to the brain. "Alzheimer's disease is a vascular disease," he said.
Data from nine studies in the United States and Western Europe that consistently corroborate a 15% decline in the incidence of new Alzheimer's cases over the past 25 years, does it added.
"Why, I think the only reasonable candidate is the improvement in vascular health," said Dr. Hofman.The most important factor is the decrease in smoking, he believes, but Rich countries are also more likely to better control high blood pressure and cholesterol levels.
Dr. Seth Love, professor of pathology at the University of Bristol in England, pointed out that one of the essential features of Alzheimer's is the reduction of blood flow. through the brain of the brain.
This happens even in people with the genetic mutation that causes Alzheimer's disease in middle age. Fifteen to twenty years before these people have dementia, the blood in their brains slows down.
"We do not know why," said Dr. Love.
Or maybe it is really amyloid that triggers the avalanche of other problems.
Some researchers still hope that if Anti-amyloid drugs are given early enough to prevent dementia. Clinical trials are currently under study in people genetically predisposed to Alzheimer's disease.
But even if the drugs work, will they work in older patients who make up the bulk of people diagnosed with Alzheimer's – but who have nothing that looks like a pure form of the disease?
Perhaps these drugs will have only a minor effect in patients with mixed pathologies, said Dr. Hardy. Huge trials would be needed for years to achieve such a minimal effect.
"This is not the kind of medicine we are looking for," said Dr. Skovronsky of Eli Lilly. "We want something that has a great effect."
Dr. Skovronsky was forced to do an examination of conscience. Trying anti-amyloid drugs in the elderly at the beginning or the middle stage of Alzheimer's disease simply does not work.
But when is it better to intervene and in whom? And should scientists also find drugs for all other pathologies in the brains of patients with dementia?
"The time has come to focus on these difficult issues," said Dr. Skovronsky.
[ad_2]
Source link