A study led by Turkish researcher Pinar Ayata unveiled a critical mechanism involving microglia—specialized immune cells in the brain—that could open new avenues for treating Alzheimer's disease, according to The Sun. The research revealed that dark microglia produce and release toxic lipids that damage neurons and oligodendrocyte progenitor cells, which are essential for brain function and are most impacted in Alzheimer's patients.
"These findings reveal a critical link between cellular stress and the neurotoxic effects of microglia in Alzheimer's disease," said co-lead author Anna Flury, according to Il Fatto Quotidiano. "Such treatments could significantly slow or even reverse the progression of Alzheimer's disease, offering hope to millions of patients and their families," added her colleague, Leen Aljayousi, according to the same source.
The study, published in the journal Neuron, emphasizes the dual role of microglia in the brain. While they act as first responders that protect neural health, some microglia exacerbate neurodegeneration and propel the progression of Alzheimer's disease. Understanding these differences has been a focal point for Ayata and her team.
Using electron microscopy, the researchers examined postmortem brain tissues from Alzheimer's patients. They found that levels of dark microglia were twice as high in Alzheimer's patients compared to healthy individuals, as reported by The Sun. This discovery sheds light on how cellular stress pathways in microglia contribute to neuronal damage through the production of toxic lipids.
Canadian neuroscientist Marie-Ève Tremblay, who co-authored the study, observed that these cells were abundant in samples from Alzheimer's patients, suggesting a role in the disease's pathology. "The state of dark microglia was a purely morphological description made by Marie-Ève Tremblay in 2016, but no one understood very well what it meant," explained neuroscientist Amanda Sierra, according to La Nación. "Now, almost 10 years later, they have been able to see that these cells are damaged in response to the harmful environment present in Alzheimer's disease and that they also contribute to the pathology."
The research offers a promising target for pharmacological therapies. "Targeting this pathway may open up new avenues for treatment by either halting the toxic lipid production or preventing the activation of harmful microglial phenotypes," said Flury, according to Il Fatto Quotidiano. Initial tests conducted on mice showed that blocking this stress response mechanism or preventing the production of toxic substances led to an improvement in symptoms.
However, some experts urge caution. "The role of microglia in the complex process of dementia is still somewhat confusing," said Belgian biologist Bart De Strooper, an expert in Alzheimer's disease, according to La Nación. "What is less clear is what changes cause neurodegeneration and which are a consequence of it; that is, whether microglia adapt to neurodegeneration or cause it," he remarked.
The study also highlights the historical significance of microglial research. In 1918, Spanish scientist Pío del Río Hortega discovered microglia by treating brain slices with silver carbonate and ammonia, observing previously unseen cells under the microscope, as reported by La Nación. His work laid the foundation for understanding these critical brain cells, and he was proposed three times for the Nobel Prize in Medicine.
According to Il Fatto Quotidiano, Alzheimer's disease affects about 40 million people worldwide, with at least 1 million cases in Italy alone, causing progressive loss of memory and dementia. With an aging global population, finding effective treatments is more urgent than ever.
Neuroscientist Amanda Sierra compares microglia to the Roman god Janus, who had two faces and was associated with war and peace. "They are cells that should defend the brain, but when impaired, they damage the neurons," she told La Nación. Recent studies suggest that microglia participate causally in the pathology of Alzheimer's, although they are not the sole cause.
The research team's findings represent an important advance in understanding Alzheimer's disease. While it's still in the early stages, the study provides a foundation for developing drugs that could slow down or even reverse dementia. This discovery offers "a promising target for pharmacological therapies that may slow down and possibly reverse" the progression of Alzheimer's disease, announced the City University of New York.
Further research is needed to fully comprehend the role of microglia in neurodegeneration. However, the identification of this stress-related pathway in microglia opens the door to potential treatments that could alleviate the burden of Alzheimer's disease on patients and their families worldwide.
This article was written in collaboration with generative AI company Alchemiq