Four Subtypes of Alzheimer's Disease Based on Differing Progression of Tau Pathology

Researchers have recently proposed a taxonomy of subtypes of Alzheimer's disease based on differences in the spread of tau protein aggregation through the brain that is characteristic of the later stages of the condition. Tau aggregation caused dysfunction and cell death in neurons. It is interesting to speculate as to the underlying reasons why there are four such classes of progression of tau pathology. Why only four? Why so clearly four? One might suggest - with absolutely no evidence to hand as of yet - that this has something to do with differing rates of age-related failure among the few drainage pathways by which cerebrospinal fluid leaves the brain, for example. This drainage allows the removal of molecular waste from the brain, its loss is implicated in Alzheimer's disease, and it is possible that drainage rates falter more or less rapidly in different parts of the brain for different people.

Alzheimer's disease is characterized by the abnormal accumulation and spread of the tau protein in the brain. An international study can now show how tau spreads according to four distinct patterns that lead to different symptoms with different prognoses of the affected individuals. "In contrast to how we have so far interpreted the spread of tau in the brain, these findings indicate that tau pathology in the brain varies according to at least four distinct patterns. This would suggest that Alzheimer's is an even more heterogeneous disease than previously thought. We now have reason to reevaluate the concept of typical Alzheimer's, and in the long run also the methods we use to assess the progression of the disease."

Researchers used a study population of 1,143 individuals who were either cognitively normal or individuals who had developed Alzheimer's in various stages. An algorithm was applied to the data from the tau PET images from the 1,143 individuals, the so-called SuStaIn (Subtype and Staging Inference) algorithm. As expected, many individuals did not show any abnormal tau PET signal, and these were therefore automatically assigned to a tau-negative group. By then cross-validating the tau PET images with a sixth independent cohort, and following up the individuals for about two years, the researchers were able to develop four patterns that best represented the data from the remaining individuals.

"We identified four clear patterns of tau pathology that became distinct over time. The prevalence of the subgroups varied between 18 and 30 percent, which means that all these variants of Alzheimer's are actually quite common and no single one dominates as we previously thought."


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