The hopeful changes against Alzheimer's want to be replicated with Parkinson's

BarcelonaIt is not the same to receive a cancer diagnosis now as it was three decades ago. Patients' prognosis is radically better and so is their quality of life. Alzheimer's and Parkinson's, on the other hand, are almost the same as 30 years ago: neurodegenerative diseases are unfortunately still irreversible and have no available cure. However, the appearance of the first approved drugs against Alzheimer's, which are reluctant to arrive in Spain, are disease modifiers, they delay its progression and are the first step towards a paradigm shift, as patients have had no therapy available until now. New and better diagnostic tools have also been developed, capable of anticipating symptoms and their evolution. This encourages professionals at the start of a revolution against these diseases, which have enough parallels to consider joint strategies in the future.

To understand how these new drugs work, one must understand how the disease acts. Alzheimer's is characterized by the unusual accumulation inside and outside neurons of a peptide (a protein fragment) called amyloid beta and of the protein known as tau. It is not known why this happens, but it is very likely what causes cells to break down and the brain to atrophy little by little. The drugs, approved in Europe – but not yet in Spain, which is negotiating the price with pharmaceutical companies – are called Leqembi and Kinsula and use antibodies to attack amyloid beta plaques and slow down the cognitive decline of people with early symptoms of the disease. There are other neurodegenerative diseases that are also characterized by the accumulation of these proteins in the brain, which is why experts are confident that they will be able to use a similar strategy to Alzheimer's in the future.

break down and the brain to atrophy little by little. The drugs, approved in Europe – but not yet in Spain, which is negotiating the price with pharmaceutical companies – are called Leqembi and Kinsula and use antibodies to attack amyloid beta plaques and slow down the cognitive decline of people with early symptoms of the disease. There are other neurodegenerative diseases that are also characterized by the accumulation of these proteins in the brain, which is why experts are confident that they will be able to use a similar strategy to Alzheimer's in the future.

"These treatments against Alzheimer's could be used against other neurodegenerative diseases", assures Carlos Cruchaga, the lead researcher of the neurogenomics and informatics group at the University of Washington, who explains to ARA that 80% of the proteins associated with the disease are associated with all neurodegenerative diseases, although each one then has unique processes. Lewy body dementia and 30% of Parkinson's cases that develop dementia also have beta-amyloid accumulation, which is why there are already studies evaluating the efficacy of lecanemab and donanemab, the two properties that use Leqembi and Kisunla respectively, to treat this type of patient.

The unusual aggregation in neurons of a protein called alpha-synuclein is a characteristic of Parkinson's, but also of 30% of Alzheimer's patients, and treatments targeting this protein are already being studied. This leads Cruchaga to believe that in the future, a combined treatment could be prescribed to attack different protein accumulations simultaneously, such as beta-amyloid and alpha-synuclein. "There are many clinical studies for Alzheimer's, Parkinson's or frontotemporal dementia that use different approaches to see if they work. I think many of these will be approved. Some will work and we will see them soon," says the expert hopefully, who was one of the speakers at the XIV Barcelona Pittsburgh Biennial Conference, organized by Ace Alzheimer Center this week in Barcelona.

Diagnosing 20 years before symptoms

The Catalan capital has been the world capital in the fight against Alzheimer's with researchers from all over the world, who have shared their work on tackling dementia, future treatments, and new diagnostic tools. In this regard, Cruchaga explains that proteins are also key for the development of diagnostic tests, especially at the beginning of the disease, when it is difficult to differentiate them because the symptoms are similar. He and his team have used artificial intelligence to develop a test that can identify the proteins that differentiate each disease, but also to quantify if a person has more than one because, in these cases, the prognosis for patients is very different.

The accumulation of these proteins, which Nikolaos Scarmeas –professor of neurology at the National and Kapodistrian University of Athens School of Medicine– describes as the "garbage" of the brain, begins between 15 and 20 years before the first symptoms appear, which generally start with memory loss. Diagnostic tools, with a simple blood test, already allow detecting the disease when this aggregation of beta-amyloid and tau begins, and the drugs being developed aim to attack this "window" of 20 years before symptoms. For now, however, they are still being tested, and the available drugs are administered to people who already have mild cases of the disease.

This presents a dilemma for Scarmeas, as the diagnosis is more advanced than the treatment and causes harm to patients. "If we identify someone at high risk of developing the disease in 20 years, but who is currently healthy, what do we tell them? To what extent is it useful to communicate it? You can cause a lot of stress and anxiety. But, on the other hand, if we detect changes in the brain, they have the right to know," the expert questions. Given the absence of a cure, Scarmeas has focused her research on how an active lifestyle creates a "kind of safety net" that makes the brain more resilient and slows the onset of symptoms. It is called cognitive reserve and is related to healthy lifestyle habits.

"Lifestyle doesn't seem to be able to combat the disease directly, but it does improve your resistance," she insists. That's why in consultations they recommend having an active social life, exercising, eating healthily, reading, sleeping well, and avoiding elements like tobacco and alcohol. "They don't solve the problem, but they act as a cushion so that the symptoms take longer to appear," she maintains. However, and while waiting for – as has happened with cancer in the last 30 years – there to be a therapeutic revolution against Alzheimer's, experts maintain that these small changes are one of the best strategies to slow the progress of the disease.