It is now known that Alzheimer’s disease begins several years before its symptoms appear. Hence the efforts made to find ways to detect the warning signs of this merciless pathology. A team from McGill University has succeeded in highlighting in healthy individuals, without memory loss or cognitive deficit, anomalies in the electrical activity of the brain that would result from an early effect of the disease.
This major discovery, which is published in the journal Nature Neurosciencewould therefore allow the administration to people with these anomalies of treatments that could delay the development of the disease. It was carried out thanks to the participation of a hundred people prone to developing Alzheimer’s, either because they carry a particular gene that predisposes them to this disease, or because members of their family have developed it.
These people are part of the PREVENT-AD cohort, set up at the Douglas Mental Health University Institute about ten years ago. “We are fortunate to have these participants who were completely healthy in terms of their cognitive functions when they entered the cohort, and who, for some of them, have unfortunately experienced memory loss or cognitive disorders over the years that lead us to believe that they are developing Alzheimer’s.”
“From a research perspective, this is an absolutely extraordinary resource and, I believe, unique in the world – in the sense that we can follow these people over several years,” emphasizes from the outset Sylvain Baillet, professor of neuroscience at the Montreal Neurological Institute-Hospital, lead author of this study alongside Sylvia Villeneuve of the Douglas Research Institute.
The participants underwent various brain scans periodically, every three to four years: a battery of tests to assess their cognitive health; a test using positron emission tomography, which shows possible plaques of beta-amyloid and tau fibers in the brain (two proteins that participate in normal brain physiology, but which, in the case of Alzheimer’s, accumulate and are not eliminated as they should); and a magnetoencephalography (MEG) scan, which measures the brain’s electrical activity with very good temporal and spatial resolution.
An acceleration, then a slowdown
The researchers thus noted an acceleration in the overall brain activity of people in whom amyloid plaques were beginning to form, compared to what was observed in control individuals of the same age who were not particularly at risk of developing Alzheimer’s disease.
“We showed that there was more rapid activity in their brains, activity in high frequencies, and that this abnormal brain hyperactivity was more marked in the regions where amyloid plaques had accumulated. In fact, this is the first time that this phenomenon has been demonstrated in humans, or even in asymptomatic individuals – that is, without cognitive impairment or memory loss. Until now, it had only been observed in animal models. [rongeurs] Alzheimer’s disease or in computer simulations of the pathology,” says the neuroscientist.
The researchers also noted that when the brains of people who were still asymptomatic showed an accumulation of not only amyloid plaques but also tau fiber tangles, the MEG instead recorded a slowdown in overall brain activity compared to normal.
Then they found that the first signs of cognitive decline occurred four to five years after the onset of this deceleration.
“There is a kind of chain reaction [qui se met en branle] when amyloid begins to accumulate and there is an acceleration of brain activity. This runaway effect would further stimulate the accumulation of amyloid, which in turn would promote the accumulation of tau. Then, this joint accumulation of tau and amyloid would synergistically lead to a decrease — below the baseline level — in brain activity that can go as far as cell death,” explains Mr. Baillet.
Detect to act earlier
All in all, this discovery should allow the detection of traces of abnormal brain activity and “premonitory” of the development of the disease in healthy people, but prone to Alzheimer’s.
And this is done using electrophysiology techniques, such as MEG or electroencephalography, which are much less “invasive” than current imaging technologies and can therefore be used as often as necessary, says Mr. Baillet.
Since “faster-than-normal brain activity is a potential warning sign of a deviation from an Alzheimer’s disease trajectory, additional testing, including imaging, may be needed to see if there is indeed amyloid buildup.” [Et si c’est le cas,] These patients could be given the treatments [dont on dispose actuellement et] which essentially target amyloid. Administered very early, these drugs could slow the accumulation of amyloid, and therefore also that of the tau protein subsequently,” the researcher suggests.
“Clinical trials have indeed shown that these drugs are even more beneficial and delay the development of the disease even more when they are administered early.” Once symptoms appear, it is often too late to obtain conclusive results.
Mr. Baillet also hopes that this discovery will inspire a new clinical trial that would consist of administering these drugs to people in whom brain activity has been observed to be accelerated or slower than normal in order to see which ones would benefit most from this early administration.