Feb 2, 2026 09:27 PM
https://www.eurekalert.org/news-releases/1115012
INTRO: As we age, we begin to lose the connections that wire up our brains—and neuroscientists aren’t sure why. It is increasingly clear, though, that the loss of synapses—the flexible and adaptive relay stations central to our brains’ ability to think, learn, and remember—is central to the rise of cognitive decline and dementia in old age.
Now, researchers supported by the Knight Initiative for Brain Resilience have discovered clues that may tie synapse loss to another hallmark of brain aging: the declining ability of brain cells to break down and recycle damaged proteins.
Published January 21, 2026, in Nature, the study shows that synaptic proteins are particularly susceptible to this age-related garbage-disposal problem: In old age, synaptic proteins break down much more slowly, they become more likely to pile up into the tangled clumps of protein characteristic of neurodegenerative disease, and they are more likely to make their way into microglia, immune cells that prune away damaged synapses.
Those findings are the latest in a series of discoveries that suggest new links between the brain’s waste management systems, microglia, and neurodegeneration—and they could yield new insights into human brain aging and neurodegeneration, said the study’s lead author, Ian Guldner, an instructor in the Department of Neurology and Neurological Sciences at Stanford Medicine.
“We know that cognitive function and synapse density both decrease in aging human brains. We also see that microglia grow more dysfunctional with age. If microglia are taking in synapses’ damaged proteins, that could be overwhelming microglia and causing them to become dysfunctional. Overall, it would be a detrimental effect to brain health,” said Guldner, who works in the lab of Knight Initiative for Brain Resilience Director Tony Wyss-Coray, the D.H. Chen Professor of Neurology and Neurological Science at Stanford Medicine, and the study’s senior author... (MORE - details, no ads)
INTRO: As we age, we begin to lose the connections that wire up our brains—and neuroscientists aren’t sure why. It is increasingly clear, though, that the loss of synapses—the flexible and adaptive relay stations central to our brains’ ability to think, learn, and remember—is central to the rise of cognitive decline and dementia in old age.
Now, researchers supported by the Knight Initiative for Brain Resilience have discovered clues that may tie synapse loss to another hallmark of brain aging: the declining ability of brain cells to break down and recycle damaged proteins.
Published January 21, 2026, in Nature, the study shows that synaptic proteins are particularly susceptible to this age-related garbage-disposal problem: In old age, synaptic proteins break down much more slowly, they become more likely to pile up into the tangled clumps of protein characteristic of neurodegenerative disease, and they are more likely to make their way into microglia, immune cells that prune away damaged synapses.
Those findings are the latest in a series of discoveries that suggest new links between the brain’s waste management systems, microglia, and neurodegeneration—and they could yield new insights into human brain aging and neurodegeneration, said the study’s lead author, Ian Guldner, an instructor in the Department of Neurology and Neurological Sciences at Stanford Medicine.
“We know that cognitive function and synapse density both decrease in aging human brains. We also see that microglia grow more dysfunctional with age. If microglia are taking in synapses’ damaged proteins, that could be overwhelming microglia and causing them to become dysfunctional. Overall, it would be a detrimental effect to brain health,” said Guldner, who works in the lab of Knight Initiative for Brain Resilience Director Tony Wyss-Coray, the D.H. Chen Professor of Neurology and Neurological Science at Stanford Medicine, and the study’s senior author... (MORE - details, no ads)