Are we treating Alzheimer's the wrong way?

▎WuXi AppTec Content Team Editor Recently, a new study in "Science-Translational Medicine" has brought new insights into the diagnosis and treatment of Alzheimer's disease.
The study found that a type of deformed and rapidly replicating tau protein is related to cognition The recession is accelerating
.

In the past, people might think that Alzheimer's disease would progress slowly over 8-10 years, but according to Professor Jiri Safar of Case Western Reserve University School of Medicine, about 10%-30% of patients experience rapid progression.
disease development
.

"In the United States alone, there are 600,000 to 1.
8 million Alzheimer's patients," Professor Safar said
.

In his view, Alzheimer's disease patients should not be generalized.
Just as cancer treatment is developing towards individualized therapy, we need to provide different diagnosis and treatment for Alzheimer's disease patients with different conditions.
What about distinguishing? Professor Safar's research experience in prions gave him some insights.
When prions are misfolded, they can continue to replicate and cause damage to the brain, so he considered whether a similar mechanism exists for tau proteins
.

To this end, the research team managed to obtain hippocampal samples from 40 patients with Alzheimer's disease.
These patients had different rates of disease progression during their lifetimes, some of which slowly lost cognitive function over many years, and others.
Rapid decline and died within three years of diagnosis
.

Image credit: 123RF They analyzed tau protein aggregates using protein conformation techniques established when studying prions
.

Since impaired hippocampal function is clearly linked to cognitive deterioration, the state of tau in the hippocampus is a good indicator of its impact
.

During the comparison, the researchers found that the core conformation of the tau protein in the brain of patients with rapidly progressive disease was different from that of other patients, and the frequency of misfolding of these tau proteins was significantly higher
.

Among the tau protein isoforms, 4R tau proteins with four microtubule-binding repeats play a more important role, accounting for approximately 80% of all abnormal tau proteins
.

Furthermore, the link between disease duration and tau does not appear to depend on the number of tau aggregates, but rather on conformationally abnormal proteins
.

▲ Hippocampal samples from patients with different rates of disease progression (Image source: Reference [2]) In vitro, researchers tried to culture tau protein samples in different samples, and those with misfolding were significantly faster.
replication, which also shows that this type of tau protein may be the real culprit of brain damage
.

The paper notes that higher levels of misfolded 4R tau in the tau protein may predict faster cognitive decline
.

"This is the first time a link has been found between the type of tau protein and disease duration, progression," said Professor Safar.
"It is now clear to us that Alzheimer's disease is not a single disease, it is more of a category, Different patients have different disease driving factors
.

"The study believes that the abnormal conformation of tau protein is one of the important factors, and patients may be able to be divided into different diseases for treatment according to this index
.

The next step for the research team is to turn the analytical tools used in the study into clinically usable applications to identify which Alzheimer's patients are at risk for rapid progression
.

Reference: [1] Findings open the way to more precise diagnoses and treatments of Alzheimer's disease.
Retrieved Jan 6th, 2021 from https://medicalxpress.
com/news/2022-01-precise-treatments-alzheimer-disease.
html[ 2] Chae Kim et al, Distinct populations of highly potent TAU ​​seed conformers in rapidly progressing Alzheimer's disease, Science Translational Medicine (2022).
DOI: 10.
1126/scitranslmed.
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