Researchers identify 4 distinct subtypes of Alzheimer’s disease

By examining brain scans of patients with Alzheimer’s disease using an artificial intelligence algorithm, an international team of neurological researchers have found that there are actually four different forms of the disease. A discovery that could pave the way for more targeted and effective treatments.

Alzheimer’s disease is characterized by the accumulation of beta-amyloid peptides and the transformation of a structural protein, the Tau protein, which aggregates abnormally throughout the cerebral cortex. These two concomitant phenomena promote neuronal degeneration. According to the World Health Organization, 50 million people have dementia today in the world; Alzheimer’s disease is believed to be the cause of 60 to 70% of cases.

Experts have always believed that the Tau protein entanglement pattern in the brains of sick people is always the same, with a few differences. But this new study, led by neurologist Oskar Hansson of Lund University in Sweden, clearly highlights four different types of the disease, which are distinguished by the location of Tau protein clumps.

Four subtypes with specific symptoms

The artificial intelligence algorithm used by the researchers was able to bring out four distinct subtypes of the disease, by analyzing the brain scans of 1,143 people (healthy or with the disease). Each of these subtypes is characterized by a very specific spatiotemporal distribution of the Tau protein. In addition, it emerges from this study that the prevalence of each of them varies between 18 and 33%, which means that these different forms are all relatively common, none predominate among the population.

Researchers have identified four subtypes of Alzheimer’s disease, each characterized by a specific breakdown of the Tau protein. © JW Vogel et al.

In the first subtype, which affects 33% of cases, the Tau protein spreads mainly in the temporal lobe – a region of the brain located behind the temporal bone, behind the temples – and affects the patient’s memory. The temporal lobe is indeed an important area for many cognitive functions, such as hearing, language, memory and vision.

In the second subtype, identified in 18% of cases, the Tau protein accumulates in other parts of the cerebral cortex. Patients suffering from this form of the disease are less prone to memory loss, but find it difficult to plan and execute actions.

In the third subtype, which corresponds to 30% of cases, the Tau protein spreads in the visual cortex, which, as its name suggests, is responsible for processing visual information; it is located in the occipital lobe, at the back of the head. Quite logically, patients with this subtype find it difficult to orient themselves, assess distances and identify shapes.

Finally, the fourth subtype, which occurs in 19% of cases, is characterized by an asymmetric distribution of the Tau protein in the left hemisphere of the brain; here, language processing is affected.

A two-year follow-up of study participants confirmed the presence of these four distinct patterns in people with Alzheimer’s disease. These results could explain why different people have different symptoms as the disease progresses. ” This would suggest that Alzheimer’s disease is an even more heterogeneous disease than previously thought. Says neuroscientist Jacob Vogel of McGill University in Canada, co-author of the study.

Towards better patient care

Alzheimer’s disease is the main form of dementia in the world today and the number of people affected continues to increase sharply as the population ages. According to the Brain Institute, nearly 1.3 million people are affected by the disease in France, with 225,000 new cases each year. This concerns 1 in 20 people from the age of 65 and more than 1 in 4 people after 85 years.

The disease causes constant loss of neurons, but scientists are still not sure exactly why this is happening. To date, there is no known cure. However, research in this area is progressing well. Previous studies have already made it possible to identify the neurons most vulnerable to the disease: excitatory neurons (which generate “action” signals in the brain) are said to be more vulnerable. This type of neuron shows an almost 50% drop in their number during the early stages of the disease.

In another study involving eight patients with the disease, a team of researchers even managed to temporarily reverse the effects (the trial only lasted two months). Thanks to an approach based on the use of electromagnetic waves, the researchers observed an improvement in cognitive performance in seven of the eight participants!

Now Hansson, Vogel and their colleagues want to extend their analyzes over a longer period, up to 10 years, to better characterize each of the identified subtypes. As Jacob Vogel points out, this new study will re-evaluate the very concept of Alzheimer’s disease and rethink the methods used to assess its progression. On the patient side, once the subtype is diagnosed, everyone will have a better idea of ​​what symptoms to expect over time.

But above all, the results recently obtained open the way to new treatments, perhaps more adapted to each form of the disease. ” This knowledge is important for physicians who assess patients with Alzheimer’s disease and also leads us to wonder if the four subtypes might respond differently to different treatments. », Emphasizes Hansson.

Nature medicine, JW Vogel et al.

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