Alzheimer’s is actually three different disease subtypes, say research

Diseases that affect the brain are seen as some of the most worrying that people can have. Among these problems is Alzheimer’s disease, an incurable disease, which gets more serious over time.

Those affected by the disease suffer from dementia or loss of some cognitive functions, such as memory, orientation, attention and language. That’s because brain cells start to die. The diagnosis, in its early stages, can help to slow the progression of the condition, but this is not always possible.

According to traditional models. Alzheimer’s disease is probably the most diverse disease. A postmortem RNA sequencing revealed three major molecular subtypes of the disease. Each of them presents itself in a different way in the brain and represents a unique genetic risk.

Knowing this, it can help researchers predict who is most vulnerable to each of these subtypes. In addition to knowing how their disease can progress and what are the most suitable treatments for them. All of this can potentially have better results.

Disease

In addition, this discovery may help explain why effective treatments for Alzheimer’s disease have been so difficult to find so far.

The research authors found that the mouse models available for research are of a specific subtype. And not all subtypes simultaneously.

“This may partially explain why the vast majority of drugs that have been successful in specific mouse models do not align with generalized human testing across all subtypes of Alzheimer’s disease. Therefore, subtyping Alzheimer’s patients is a critical step towards precision medicine for this devastating disease, ”said the researchers.

Traditionally, Alzheimer’s disease is believed to be marked by clusters of beta-amyloid plaque (Aβ) and by tangles of tau proteins (NFTs) found in postmortem biopsies of the brain.

These two markers are synonymous with the disease. However, in recent years, the main hypotheses about what they actually do to the human brain have been questioned.

Study

It is generally believed that the accumulations of Aβ and NFT lead to neural and synaptic loss. After that comes degeneration, including inflammation and degeneration of the protective lining of nerve cells. This causes the signals in the brain to decrease.

However, the new evidence showed that up to a third of patients with a confirmed clinical diagnosis did not have Aβ plaques on their postmortem biopsies.

With the knowledge of all the research it is highly likely that there are specific subtypes of Alzheimer’s disease that have not yet been separated. And this new research helped to reveal three main strands.

For the study, the researchers analyzed 1,543 transcriptomes, which are the genetic processes being expressed in the cell, in five regions of the brain. With the RNA sequencing they were able to profile these transcriptomes. And they identified three major molecular subtypes of Alzheimer’s disease.

They are: susceptibility to tau-mediated neurodegeneration; amyloid-β neuroinflammation; synaptic signaling; immunological activity; organization of mitochondria; and myelination.

These subtypes were independent of the age and severity of the disease. Molecular signatures were also present in all regions of the brain, but specifically in the hippocampus. This region is well associated with the formation of new memories.