Researchers from New York’s Mount Sinai Medical Center reported the discovery of three main subtypes of Alzheimer’s disease. The test results were published by Science magazine.
During the study, scientists conducted RNA sequencing for over 1.5 thousand samples taken postmortem from five parts of the brain. More than a hundred patients with Alzheimer’s disease were compared with patients without the disease.
Researchers have discovered Alzheimer’s disease subtypes A, B1, B2, C1, and C2. They were combined into three larger classes – typical (C), intermediate (B), atypical (A), which are characterized by various combinations of disorders. The hippocampal region showed the strongest signal, although subtype-specific effects were found in all brain regions examined.
As the authors of the publication point out, the manifestation of Alzheimer’s disease before cognitive impairment is the formation of beta-amyloid plaques and neurofibrillary tangles, which are usually detected on post-mortem biopsy and are used to confirm the diagnosis. However, new scientific evidence points to a more heterogeneous nature of the disease, in which different pathological mechanisms are involved. The authors cite evidence that up to a third of patients with Alzheimer’s disease do not exhibit beta-amyloid accumulation, and many of those diagnosed with the disease after death had no previous history of cognitive impairment.
In class C subtypes, the researchers observed higher densities of amyloid plaques compared with classes A and B. Gender, ethnicity, age at death, and level of cognitive decline did not differ significantly between subtypes, the authors said. In addition, the types did not depend on the severity of the disease.
At the same time, scientists have found that the animal models used in modern trials correspond to the detected subtypes, but not all. This may partly explain why many drugs that have been successfully tested in such models have failed to further confirm their results in humans.
According to the researchers, identifying the subtypes revealed a variety of new signaling pathways that are disrupted in Alzheimer’s disease, as well as potential targets. In this regard, the authors believe that identifying subtypes is an important step for the development of personalized drugs. In addition, if confirmed in further trials, the discovery will lead to the identification of new biomarkers and clinical features that can be used to determine subtypes of Alzheimer’s disease during life.
As MV reported, in 2019, Alzheimer’s disease was included for the first time in the list of the most common causes of death according to the World Health Organization. Along with other forms of dementia, the disease took third position on the list.