A new study published in Molecular Psychiatry has uncovered a possible chain of cause-and-effect events that may lead to Alzheimer’s disease, offering fresh clues about how the condition develops and progresses.
Researchers from Baylor College of Medicine, the Duncan Neurological Research Institute at Texas Children’s Hospital, and collaborating institutions combined analyses of human brain tissue with laboratory experiments in fruit flies to better understand what happens inside the brain during the disease.
Alzheimer’s disease is marked by the buildup of amyloid plaques and tau tangles—abnormal protein clumps that damage brain cells and lead to memory loss and cognitive decline.
Scientists have long known about these features, but the precise steps connecting them to brain cell death have remained unclear.
To investigate, the research team studied gene activity in brain tissue from people who had died with Alzheimer’s and compared it with healthy brains.
Previous large-scale research had already identified dozens of networks of genes whose activity changes in Alzheimer’s, particularly those involved in the immune system and communication between brain cells.
However, scientists did not know which changes actually drive the disease and which are simply side effects.
To answer this, the team turned to fruit flies, a common laboratory model that shares many basic biological processes with humans. Researchers tested hundreds of genes that showed altered activity in Alzheimer’s brains by changing those same genes in flies and observing the effects on brain cells.
They found that increasing the activity of certain immune-related genes—similar to what occurs in Alzheimer’s brains—worsened nerve cell damage in the flies. This suggests that these immune genes may actively contribute to the disease rather than just reacting to it.
The researchers also made a surprising discovery about genes that control communication between brain cells, known as synaptic genes. In Alzheimer’s brains, the activity of these genes is reduced.
Scientists initially thought this reduction happened because brain cells were dying. But experiments in fruit flies showed that lowering these genes actually helped protect brain cells from damage.
This unexpected result suggests the brain may be trying to defend itself. Previous studies indicate that brain cells can become overactive early in Alzheimer’s. Reducing communication between cells might be the brain’s attempt to calm this harmful hyperactivity.
Based on their findings, the researchers propose a two-stage model of the disease. Early on, amyloid plaques may trigger excessive activity in brain cells, causing damage. Later, as tau tangles form, the brain reduces synaptic activity in a protective effort. Unfortunately, this response appears to come too late to stop the disease from progressing to dementia.
The study provides a clearer picture of the biological cascade behind Alzheimer’s and identifies specific genes and pathways that could be targets for future treatments. While more research is needed, the findings bring scientists one step closer to understanding—and potentially interrupting—the processes that lead to this devastating disease.
