New Study: Alzheimer’s Disease – Four Distinct Subtypes

Alzheimer’s disease is characterized by abnormal proliferation and accumulation of the tau protein in the brain. An international study now shows how tau spreads according to four distinct patterns that lead to different symptoms with different expectations for affected individuals. The study has been published in the journal Nature Medicine.

In contrast to how we have thus far interpreted the prevalence of tau in the brain, the results of this study show that the pathology of tau in the brain varies according to four different patterns. This means that Alzheimer’s disease is a more heterogeneous disease than previously thought, which gives us reason to re-examine the concept of typical Alzheimer’s disease and in the long term also the methods we use today to assess Disease progressionAnd the Lead author of the study, says Jacob Vogel of McGill University.

Tau proliferation in the cerebral cortex is an important marker of Alzheimer’s disease. In recent years, it has become possible to monitor the storage of harmful protein in the brains of living people with the help of PET, an advanced medical imaging technology.

Over the past thirty years many Researchers describe the development of the Tau pathology in Alzheimer’s disease using one model, despite repeated patient cases that do not fit the model. However, the current results explain why different types of patina have different symptoms.

– Since different brain regions are affected differently in the four subgroups, patients have different symptoms and also have different expectations. This knowledge is important for clinicians investigating Alzheimer’s patients, and it opens new research to study whether the four different subgroups of Alzheimer’s disease may respond differently to different treatments. Oscar Hanson, chief physician at University Hospital of Skåne and professor of neuroscience at Lund University and the MultiPark Strategic Research Area, who led the study, says.

The complete clinical picture of Alzheimer’s disease

The current study is a collaboration between researchers in Sweden, Canada, the USA and Korea. Together, the researchers screened the largest and most diverse population in the world to date using tau PET that covers the complete clinical picture of Alzheimer’s disease. The study included participants who had not yet had time to develop any symptoms, the so-called Alzheimer’s disease before symptoms, participants with mild memory difficulties, and participants with fully advanced Alzheimer’s dementia.

In the first sample, long-term data from 1,612 individuals were pooled in five independent multicenter studies. Among these, researchers identified a total of 1,143 individuals who were either cognitive normal or individuals who developed Alzheimer’s disease at different stages.

The data containing the Tau PET images of 1,143 individuals were entered into a computer and the researchers applied a data algorithm, called SuStaIne (subtype and staging inference). The material was processed by researchers using machine learning in an automated process, in order to be able to distinguish between subgroups and different patterns in a neutral way as possible.

As expected, several individuals showed no abnormal tau PET signal and thus were automatically assigned to the negative tau group. By validating the tau PET images with an independent sixth cohort and following the individuals for approximately two years, the researchers were able to develop four patterns that better represent data from the remaining individuals. Although the number of subgroups differed for individuals, all were represented in all cohorts.

We identified four distinct pathways of Tau pathology that characterized over time in which the prevalence of different subgroups varied between 18 and 30 percent, which means that all of these variants of Alzheimer’s disease are actually very common and no one dominates quite as well as we had previously thought, Oscar Hanson.

Researchers believe it is important to better understand why the differences are different for individuals with Alzheimer’s disease. In the study, they systematically describe how the four different variants of Alzheimer’s disease differ from years in terms of how tau spreads and what symptoms occur.

• The first alternative: The tau is mainly spread Within Temporal lobe mainly affects memory. The first alternative occurred in 33 percent of all cases.
• The second alternative: Unlike the first variant, this variant spreads throughout the rest of the cerebral cortex. The individual suffers from fewer memory problems compared to the variable, despite the greater difficulties in executive functions / abilities, or the ability to act which relate to thinking, planning and carrying out an action. The second option occurred in 18 percent of all cases.
• The third alternative: The tau is stored in the back of the brain in the visual cortex, that is, in the back of the brain where information from the optic nerve is processed and classified. The visual-spatial processing in the brain is affected by perceptual impressions in individuals with this distribution pattern who find it difficult, for example, to orient themselves, distinguishing shapes and lines, distance, movement, and place of objects in relation to each other. The third variant occurred in 30 percent of all cases.
• Fourth alternative: The tau is spread asymmetrically in the left hemisphere and mainly affects the language ability of the individual. The fourth variant occurred in 19 percent of all cases.

The broad and vastly diverse base of tau-PET that exists today, along with newly developed methods of machine learning that can be applied to large amounts of data, made it possible for us to detect and distinguish these four subgroups of Alzheimer’s disease however, we will need to follow up. Longer than five to ten years so that we can better confirm the four transmission patterns of the pathology of Tau, says Oscar Hanson.

Researchers believe that Tau can best describe Alzheimer’s disease through a computer-driven model that includes spatiotemporal patterns – that is, it sees patterns across time and space. They believe that their findings are important to reassess the disease and that this new knowledge in the future could give patients more individualized treatment modalities.For more information about the study, contact:
Oscar Hanson, Professor of Neuroscience in the Clinical Memory Research Unit at Lund University and Chief Physician at Skien University Hospital, [email protected], 0722-26 77 45.

Publishing
“Four distinct pathways for determining tau depositionis beingEd in Alzheimer’s disease“
Natural Medicine April 29, 2021. https://www.nature.com/nm/

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Contact the press at Lund University School of Medicine: Katrin Ståhl, 046-222 01 31, 0725-27 97 97, [email protected]

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