Researchers at the Advanced Science Research Center at the CUNY Graduate Center have made a significant discovery in understanding Alzheimer’s disease. The study, published in the journal Neuron, highlights microglia, the brain’s primary immune cells, as central players in both the protective and harmful responses associated with the disease.
Microglia play a double-edged role in Alzheimer’s pathology. While some protect brain health, others worsen neurodegeneration. To understand this complex relationship, the research team, led by Dr. Pinar Ayata, aimed to identify the “harmful microglia” in Alzheimer’s disease and develop therapeutic targets.
The study revealed a novel neurodegenerative microglia phenotype characterized by an integrated stress response (ISR) pathway. Activation of this pathway prompts microglia to produce toxic lipids that damage neurons and oligodendrocyte progenitor cells, leading to synapse loss and accumulation of neurodegenerative tau proteins.
Blocking the ISR pathway or lipid synthesis reversed symptoms of Alzheimer’s disease in preclinical models. The researchers identified an accumulation of “dark microglia” in postmortem brain tissues from Alzheimer’s patients, which were present at twice the levels seen in healthy-aged individuals.
The study’s findings highlight a critical link between cellular stress and the neurotoxic effects of microglia in Alzheimer’s disease. Targeting this pathway may open up new avenues for treatment by halting toxic lipid production or preventing harmful microglial phenotypes.
This breakthrough research underscores the importance of understanding the cellular underpinnings of Alzheimer’s disease and emphasizes the role of microglial health in maintaining overall brain function.
Source: https://www.labmate-online.com/news/Laboratory-research-news/126/breaking-news/alzheimers-cellular-mechanism/63701