New Alzheimer's hope as study finds 'key to reversing disease'

The research could improve outcomes (Image: Alamy/PA)

In a new discovery in the battle against Alzheimer's disease, scientists have pinpointed a key cellular mechanism that is the primary cause of the neurodegenerative condition. American scientists from the Advanced Science Research Center at The City University of New York (CUNY ASRC) have identified how cellular stress in the brain correlates with the advancement of dementia.

Their findings, now published in the journal Neuron, suggest there might be a "promising" new target for medicinal interventions that could decelerate or potentially reverse Alzheimer's. The groundbreaking research highlighted microglia—considered the brain’s immune cells—as pivotal in both protective and detrimental responses in the condition’s development.

Microglia, often referred to as the brain’s “first responders”, are currently acknowledged as a critical factor in Alzheimer's disease progression. Yet, despite their crucial role, these cells are notorious for their paradoxical nature: some microglia safeguard brain health while others escalate neurodegeneration.

Deciphering the operational differences between these two microglial populations has been central to the work of Professor Pinar Ayata, the study’s lead researcher.

Professor Ayata commented on the significance of the research, stating: "We set out to answer what are the harmful microglia in Alzheimer's disease and how can we therapeutically target them. We pinpointed a novel neurodegenerative microglia phenotype in Alzheimer's disease characterised by a stress-related signalling pathway."

The research team discovered that activation of this stress pathway, known as the integrated stress response (ISR), prompts microglia to produce and release toxic lipids. The lipids damage neurons and oligodendrocyte progenitor cells - two cell types essential for brain function and most impacted in Alzheimer's disease.

Blocking the stress response or the lipid synthesis pathway reversed symptoms of Alzheimer's in preclinical models. Using electron microscopy, the research team identified an accumulation of "dark microglia" - a subset of microglia associated with cellular stress and neurodegeneration, in postmortem brain tissues from Alzheimer's patients.

The cells were present at twice the levels seen in healthy-aged people. Study co-lead author Anna Flury said: "These findings reveal a critical link between cellular stress and the neurotoxic effects of microglia in Alzheimer's disease."

The research team say their study highlights the potential of developing drugs that target specific microglial populations or their stress-induced mechanisms.

Co-lead author Leen Aljayousi from Prof Ayata's lab added: "Such treatments could significantly slow or even reverse the progression of Alzheimer's disease, offering hope to millions of patients and their families."