Rising levels of a protein tied to Alzheimer's disease may show up as depression years before memory problems set in, according to a new study that suggests changes in mood could serve as an early warning sign of brain deterioration in older adults. The research, published in The Journal of Neuroscience, found that as levels of a protein called tau increased in cognitively healthy older people, so did their depressive symptoms. The pattern did not hold in people who already had mild cognitive impairment or Alzheimer's disease, suggesting the link between tau and mood may be strongest in the earliest stages of brain change—before other symptoms appear.
"We are able to show these subtle but meaningful temporal associations between tau accumulation and declines in mood, as they give us important insights into understanding the underlying mechanisms of the emergence of these symptoms," the study's lead author, Teodora Markova of Brandeis University, told Newsweek. "Declining mood and worsening depressive symptoms in aging are associated with an increased risk of going on to develop Alzheimer’s disease dementia. "Our results suggest that the emergence of depressive symptoms may actually be a symptom of accumulating pathology." Markova and her colleagues used data from the Alzheimer's Disease Neuroimaging Initiative, a long-running research effort that tracks older men and women with and without cognitive problems such as memory, attention and thinking difficulties.
Participants underwent repeated brain scans designed to detect tau, along with questionnaires measuring depressive symptoms, across multiple visits over time. Among people whose cognitive skills were still intact, the researchers found that the pace at which tau built up in the brain was tied to how quickly depressive symptoms rose. Higher tau levels also predicted higher scores on the depression questionnaires in this group.
Notably, none of these patterns appeared in participants who had already been diagnosed with mild cognitive impairment or Alzheimer's disease. The researchers said this points to tau buildup as something that comes before, and likely contributes to, worsening depression—rather than the other way around. "Future work can continue to track how participants' tau levels and depression symptoms evolve over longer periods of time, particularly as some develop cognitive impairment or more clinically significant levels of depression," Markova said, in a statement accompanying the study.
"Continuing to follow these trajectories, observing how early mood changes relate to later clinical outcomes, and establishing relationships with other methods tracking the development of Alzheimer's disease will provide more clarity on methods to determine which individuals may be at an increased risk." Tau is one of two proteins, along with amyloid, most closely associated with Alzheimer's disease. As it accumulates in the brain, it is thought to disrupt communication between brain cells, contributing to memory loss and cognitive decline. The researchers say their findings suggest that monitoring depressive symptoms as people age could complement existing tools, such as brain scans and cognitive testing, in identifying who may be at heightened risk of neurodegenerative disease.
Because the association appeared before cognitive symptoms emerged, tracking mood changes over time could potentially flag at-risk individuals earlier than current methods allow. The researchers now say that longer-term studies are needed to confirm whether early mood changes reliably predict later cognitive decline, and how tracking depression alongside other biological markers might sharpen risk assessments for Alzheimer's disease. "I am hopeful that this inspires more work leveraging these large-scale datasets to continue linking imaging biomarkers to neuropsychiatric symptoms," Markova said.
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