Rising levels of tau, one of the two hallmark proteins of Alzheimer's disease, appear to precede an increase in depressive symptoms in older adults whose memory and thinking are still intact. That is the central finding of a study published in JNeurosci by Teodora Markova of Brandeis University and colleagues, who examined how the two trajectories moved together over time.
The team drew on data from the Alzheimer's Disease Neuroimaging Initiative, a long-running study in which older participants undergo repeated brain imaging and complete standardized questionnaires at multiple visits. Among people without cognitive deficits, the pace of tau accumulation tracked with how quickly depressive symptoms climbed, and higher tau levels predicted higher scores on the depression measure at later points. The sequence - tau first, mood symptoms after - is what led the researchers to conclude that tau buildup likely contributes to the depressive symptoms rather than the reverse.
The pattern did not appear in participants who already had mild cognitive impairment or Alzheimer's disease. That contrast points to a fairly narrow window early in the disease process, before measurable cognitive change, when mood shifts may carry information about what is happening in the brain. The researchers suggest that following depressive symptom trajectories in aging populations could sit alongside existing tools for gauging who is at elevated risk of neurodegenerative disease.
This is an observational analysis of existing cohort data, and the authors are clear that longer follow-up is needed. Tracking the same participants as some go on to develop cognitive impairment or clinically significant depression, and comparing these trajectories against other Alzheimer's biomarkers, will be required before early mood changes could be used to flag individual risk.