Alzheimer's: TREM2 is said to delay the emergence of this disease
Researchers at the German Centre for Neurodegenerative Diseases (DZNE) and the Institute for Research on Brain Diseases and Dementias (ISD) have discovered that a protein called TREM2 can have a mitigating effect on the progression of Alzheimer's disease.
TREM2 a key factor
In a new study led by Professor Christian Haass and Professor Michael Ewers, patients with higher levels of TREM2 in their cerebrospinal fluid at different stages of the disease have a better prognosis than those in whom this protein is present in lower amounts. An observation that provides a starting point for the development of new therapeutic strategies.
In the brain, TREM2 is produced exclusively by microglia, which serves as immune cells for this organ. These cells patrol the brain, eliminating cellular waste and abnormal extracellular deposits. Previous studies by Haass and colleagues in mice had shown that TREM2 activated microglia to selectively lock up and destroy toxic protein aggregates typical of Alzheimer's disease.
TREM2 would protect the brain from the effects of Alzheimer's disease
These observations suggest that TREM2 may protect the brain from the degenerative effects of Alzheimer's disease - at least in the mouse model. But can these results be extended to patients with Alzheimer's disease? Does TREM2 also have a protective effect on the human brain? In previous work, teams led by Haass and Ewers had also shown that the concentration of TREM2 was high in cerebrospinal fluid samples collected from patients with Alzheimer's disease,
This would probably be due to the activation of the microglia in response to the pathological changes associated with this disease. However, the crucial question remained unresolved: do higher levels of TREM2 represent a protective or deleterious response to these changes?
They sought to establish a statistical correlation
To answer this question, Ewers, Haass and their colleagues sought to establish a statistical correlation between the concentration of TREM2 in cerebrospinal fluid samples collected from their patients and the rate of disease progression in these individuals over several years. They used data from 385 patients collected in the Alzheimer's Disease Neuroimaging Initiative (ADNI).
A large clinical data set including medical records and samples taken not only from patients with Alzheimer's disease, but also from healthy elderly people, which are examined regularly over many years. These data should make it possible to identify any significant association between specific biochemical changes and the clinical course of Alzheimer's disease.
Indeed, Ewers und Haass was able to confirm that higher concentrations of TREM2 were associated with a more favourable prognosis at all stages of the disease. In these subjects, memory was less unstable and the rate of narrowing of the hippocampus - an area of the brain that plays an essential role in learning and memory - was less pronounced.
Clinically relevant results
"Our results are clinically relevant because these patients were at risk of developing systematically reduced dementia over an 11-year period," says Ewers. "However, the activation of the microglia is a double-edged sword. In addition to providing protective effects, this can lead to inflammatory processes. Nevertheless, TREM2 could play a key role in triggering a protective immune response in the brains of Alzheimer's disease patients. »
The concentration of TREM2 in the cerebrospinal fluid generally increases during the early stages of the disease, when the first symptoms appear. "The production of TREM2 is a response to an existing brain injury," explains Haass. "This protein stimulates the microglia to protect the brain. »
An antibody that will stimulate the function of TREM2 and its protective effect
However, this protection does not seem sufficient in patients with Alzheimer's disease. "This is where Haass and his colleagues see an option for new therapeutic strategies. "We are currently developing a therapeutic antibody that will stimulate the function of TREM2 and thus improve its protective effect," he said.
