Alzheimer’s: inflammation of brain tissue involved in disease progression

First neurodegenerative disease in France, Alzheimer’s disease affects nearly one million people. This form of age-related dementia gradually and irreversibly leads to dysfunction and then death of nerve cells in the brain.

Two phenomena have been identified by the research. First, beta-amyloid plaques accumulate abnormally in neurons, causing brain damage. This is followed by neurofibrillary tangles of Tau protein that clog the interior of neurons, particularly those in the entorhinal cortex responsible for the formation of memories and memory.

Until now, researchers thought that these two phenomena were responsible for the neuroinflammation of neurons. This is due to the activation of resident immune cells in the brain, called microglial cells. But in a study published in the journal Nature Medicine, researchers from the University of Pittsburgh School of Medicine (USA) showed that this neuroinflammation is actually the main driver of the spread of the Tau protein.

A key role of neuroinflammation in the development of Alzheimer’s

Although studies in cultured cells and laboratory animals have accumulated ample evidence that microglial activation drives the spread of tau fibers in Alzheimer’s disease, this process has never been proven in humans. .

Here, researchers used live imaging to examine the brains of people with different stages of Alzheimer’s disease and healthy older adults in depth. They then found that neuroinflammation was more prevalent in older people and was even more pronounced in patients with mild cognitive impairment and those with dementia associated with Alzheimer’s disease. Bioinformatics analysis confirmed that tau propagation is dependent on microglial activation – a key element linking the effects of beta-amyloid plaque aggregation to tau propagation and, ultimately, disorders cognition and dementia.

“Many older people have beta-amyloid plaques in their brains but never progress to the development of Alzheimer’s disease, points out Tharick Pascoal, assistant professor of psychiatry and neurology and lead author of the study. We know that amyloid accumulation alone is not enough to cause dementia – our results suggest that it is the interplay between neuroinflammation and amyloid pathology that triggers the spread of tau and ultimately leads to extensive brain damage and cognitive impairment.”

According to the study authors, this finding suggests that a treatment specifically targeting neuroinflammation could be effective in people with early-stage Alzheimer’s disease since it could help reverse or at least slow down the accumulation of pathological tau protein in the brain and prevent dementia.

“Our research suggests that a combination therapy aimed at reducing amyloid plaque formation and limiting neuroinflammation may be more effective than treating each condition individually.”concludes Professor Pascoal.