Depression in later life may be an early warning from the brain, appearing years before Alzheimer’s begins to affect memory and thinking
A new study in JNeurosci found that faster accumulation of tau, a protein closely tied to Alzheimer’s, was associated with worsening depressive symptoms in older adults who remained cognitively healthy. Teodora Markova of Brandeis University and her colleagues investigated whether changes in mood might track the gradual buildup of tau in the aging brain.
Tau normally helps support the internal structure of neurons. When it becomes abnormal, however, it can collect into tangles that interfere with brain function. These tangles are one of the defining biological features of Alzheimer’s disease, alongside deposits of amyloid beta.
Tau Buildup Tracks Worsening Depression
The researchers analyzed data from older men and women participating in the Alzheimer’s Disease Neuroimaging Initiative. Over multiple visits, participants underwent brain imaging designed to detect tau and completed questionnaires measuring depressive symptoms.
Among people without cognitive (memory, attention, and thinking) deficits, the rate of tau accumulation was linked to how quickly depressive symptoms increased. Higher tau levels also predicted higher scores on later depression assessments.
The sequence of these changes led the researchers to suggest that tau buildup may precede and potentially contribute to worsening depressive symptoms. The findings do not establish that tau directly causes depression, but they point to a biological connection that may emerge before measurable cognitive decline.
A Pattern Limited to Early Brain Changes
Notably, the same relationship was not detected in participants with mild cognitive impairment or Alzheimer’s disease. One possibility is that once cognitive symptoms develop, other brain changes, medical problems, medications, or the emotional effects of declining health may make the relationship between tau and depression more difficult to isolate.
The results also highlight the varied nature of depression in older adults. Mood symptoms can arise from many causes and should not be treated as proof of Alzheimer’s disease. However, monitoring how depression changes over time could complement brain imaging, cognitive testing, and other tools used to identify people who may face a higher risk of neurodegeneration.
Markova said, “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. 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.”
Reference: “Tracking the Continuous Time Dynamics of Tau and Depressive Symptoms Across the Alzheimer’s Disease Continuum” by Teodora Z. Markova, Margo B. Heston, Anne S. Berry and for the Alzheimer’s Disease Neuroimaging Initiative, 23 August 2026, Journal of Neuroscience.
DOI: 10.1523/JNEUROSCI.2309-25.202
This study was funded by the National Institute on Aging.
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