An investigation turns the origin of Alzheimer’s and proposes a different cause than what was believed

The study questions the main target of the vast majority of trials: it is not the beta-amyloid plaques, but the levels of the protein. They have verified that, aside from the plaques, people with low levels of this protein are more likely to suffer from cognitive deterioration”Many of us accumulate beta-amyloid plaques in the brain as we age, but very few develop dementia”The main thesis on the cause of Alzheimer’s, again, questioned. The theory that Alzheimer’s is caused by the buildup of beta-amyloid protein plaques in the brain has guided the search for a cure for this disease for decades. No success at the moment. A new essay questions whether this is the correct approach. What we lose is more important than what we gain “We saw that people who already accumulate plaques in their brains and who are capable of generating high levels of soluble beta-amyloid have a lower risk of developing dementia within three years,” he says. in that magazine Alberto J. Espay, one of the authors of the study. His study found that, with a starting level of soluble amyloid beta in the brain greater than 270 picograms per milliliter, people can remain cognitively normal, regardless of the amount of amyloid plaques in their brains. “It is very logical – if one puts aside the prejudices that we have created for too long – that a neurodegeneration process is caused by something we lose, beta-amyloid, instead of something we gain, amyloid plaques,” he explains. Professor of Neurology at the University of Cincinnati School of Medicine (USA). “Degeneration is a process of loss, and what we lose turns out to be much more important.” Brains With Plaques But Without Dementia For the past hundred years, there has been a consensus that Alzheimer’s was caused by the buildup of amyloid plaques in the brain. But Espay and his team hypothesized that the plaques themselves are not the cause. They posit that the levels of soluble beta-amyloid in the brain decrease as it accumulates in plaques. The problem is not the plaques themselves, but the decrease in soluble protein in the brain. This protein decreases under situations of biological, metabolic or infectious stress, and is transformed into amyloid plaques. But the researchers had already detected something paradoxical. “The paradox is that “many of us accumulate plaques in the brain as we age, but very few, even with plaques, develop dementia.” Despite this, he warns, “plaques remain the focus of our attention in regarding the development of biomarkers and therapeutic strategies.” Opening other therapeutic targets This is something that has been drawing the attention of several researchers for some time. A month ago, for example, Spanish researchers told us that the problem of current trials in Alzheimer’s is that many of those who participate are “patients who are believed to develop Alzheimer’s but later do not develop it. And that this happens, among other things, because it is being seen that “that protein also accumulates in healthy aging, for example”, warned Marta Barrachina, a specialist in neurodegenerative diseases. “The fact of having accumulated beta-amyloid does not always mean that you evolve to Alzheimer disease”. The researcher explained that, for this reason, the focus is now being broadened and investment is being made in projects “that try to find other therapeutic targets.” Reducing beta-amyloid levels “can be toxic” What Espay has done, together with Andrea Sturchio, from the Department of Clinical Neuroscience at the Karolinska Institute in Sweden, is analyzing beta-amyloid levels in a group of patients with mutations that make them more likely to develop amyloid plaques in the brain, that is, more likely to develop Alzheimer’s . And what they saw is the same as what they had seen in previous studies with the general population. That, apart from the accumulation of plaques in the brain, people with high levels of soluble beta-amyloid were cognitively normal, while those with low levels of this protein were more likely to suffer from cognitive impairment. Beta-amyloid protein works in soluble form in the brain, but there are times when it hardens and forms those amyloid plaques. Sturchio stresses that many of the trials in recent years have focused on reducing amyloid plaques in the brain. And some have succeeded, but they have not been successful as a treatment for Alzheimer’s disease. What’s more, most patients did worse in trials that reduced levels of soluble beta-amyloid in their brains. “I think this is the best evidence that reducing the soluble level of the protein can be toxic,” Sturchio warns in the Journal of Alzheimer’s Disease. Findings that can be extrapolated to Parkinson’s? Her conclusions represent a new twist to the dominant theory so far in Alzheimer’s research. Researchers are now studying whether increasing levels of soluble beta-amyloid in the brain could be a beneficial therapy for Alzheimer’s patients. Making sure, yes, that increasing the levels of that protein does not mean that they become amyloid plaques. At the same time, they try to understand the origin of the disease: what causes the levels of soluble amyloid beta to decrease. If it is a virus, a toxin, a nanoparticle, a biological or genetic process… And they go even further. Because they believe that their findings can be extrapolated to other neurodegenerative diseases. In Parkinson’s disease, for example, a normal soluble protein in the brain called alpha-synuclein can harden into a deposit called a Lewy body. Researchers now hypothesize that Parkinson’s is not caused by the buildup of Lewy bodies in the brain, but rather by a decrease in levels of soluble alpha-synuclein. “We believe that what may be more important in all degenerative diseases is the loss of normal proteins, instead of a fraction of abnormal proteins”, explains Espay. “The net effect is a loss, not a gain, of protein, as the brain shrinks as these diseases progress.”