Some cells that perform immune functions in the brain can both stop and worsen the progression of Alzheimer’s disease (depending on the specific type). The research, led by the CUNY Graduate Center in New York (USA), could open up a therapeutic future (but the road is still long)
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The researchers of CUNY Graduate Center Of New York (USA) have revealed a critical linking mechanism cellular stress in the brain to the progression of Alzheimer’s disease (AD), discovering that microglia, the brain’s main immune cells, can both stop and worsen the progression of the disease Alzheimer’s disease (depends on the type). The search could open up to a therapeutic future (but there is still a long way to go).
In other words, some populations of microglia are helpful, others are trigger worsening mechanismsaccelerating the progress of cellular degeneration. This research aimed precisely at understanding the functional differences between these populations.
Alzheimer’s disease
As our Higher Institute of Health explainsThe Alzheimer’s disease today it affects around 5% of people over 60 and in Italy it is estimated at around 500 thousand sick. It is the most common form of senile dementiawhich implies serious difficulties for the patient in carrying out normal daily activities. In particular, the disease affects memory and cognitive functions, affects the ability to speak and think but can also cause other problems, including states of confusion, mood changes and space-time disorientation.
The disease, of a neurodegenerative type, is progressive and manifests a sneaky start: People, at first, begin to forget some things, and often these first symptoms are not recognized as indicative of its onset.
Only later does everything become clearer, to reach the point where the sick can no longer not even recognize family members and they need help with even the simplest daily tasks.
The study
We set out to answer what are harmful microglia in Alzheimer’s disease and how we can target them therapeutically – explains Pinar Ayata, who led the research – We have identified a new neurodegenerative phenotype of microglia in Alzheimer’s disease characterized by a stress-related signaling pathway
The research team found that the activation of this stress pathway, known as integrated stress response (ISR)pushes microglia to produce and release toxic lipids, which damage neurons and oligodendrocyte progenitor cells, two types of cells essential for brain function and most affected by Alzheimer’s disease. Blocking this stress response or lipid synthesis pathway, according to scientists, can reverse the symptoms of the disease.
The research was conducted using the electron microscopyidentifying an accumulation of “dark microglia,” a subset of microglia associated with cellular stress and neurodegeneration, in brain tissues post-mortem of patients with Alzheimer’s, in which this subset was found at double levels compared to what is known in healthy individuals.
These results reveal a critical link between cellular stress and the neurotoxic effects of microglia in Alzheimer’s disease – explains Anna Flury, who collaborated on the study – Targeting this pathway could open new avenues for treatmentblocking the production of toxic lipids or preventing the activation of harmful microglial phenotypes
Still a long road
This research highlights the potential of drug development that target specific microglial populations or their stress-induced mechanisms.
Such treatments could slow down significantly or even reverse the progression of Alzheimer’s diseaseoffering hope to millions of patients and their families
the other co-author explains about this Leen Aljayousi
The study represents a important step forward in understanding the cellular basis of Alzheimer’s and highlights the importance of microglial health in maintaining overall brain function.
But for one true and effective therapythe road is still very long.
The work was published on Neuron.
Sources: CUNY Graduate Center / Neuron
