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Tau in Late-Life Depression: A Systematic Review and Meta-Analysis
Eric E Brown1,2, Yusuke Iwata1,2, Jun Ku Chung1,3,2
1Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Abstract:
A lifetime history of major depressive disorder (MDD) increases the risk of developing Alzheimer's disease, of which neurofibrillary tangles due to abnormal tau proteins are a hallmark. We systematically reviewed the literature on tau in MDD and identified 49 relevant articles spanning a number of modalities, including cerebrospinal fluid (CSF) analysis, positron emission tomography, and clinicopathological correlation. We compared CSF total and phosphorylated tau proteins in MDD and controls using a meta-analytic approach. We found no difference in total or phosphorylated tau in MDD. We also found no difference in a comparison of a subgroup excluding studies with significant age differences. Positron emission tomography studies lacked specificity. Clinicopathological studies failed to associate neurofibrillary tangles with MDD. The available data on tau in MDD is limited. The involvement of tau in a subset of MDD cannot be ruled out and requires prospective exploration.
Insights
Major depressive disorder (MDD) may not be directly linked to abnormal tau proteins, a hallmark of Alzheimer's disease. Current research shows no significant differences in tau levels between MDD patients and controls, suggesting limited tau involvement in MDD.
Area of Science:
- Neuroscience
- Psychiatry
- Biochemistry
Background:
- Major depressive disorder (MDD) is a known risk factor for Alzheimer's disease (AD).
- Abnormal tau proteins forming neurofibrillary tangles are a key pathological feature of AD.
Purpose of the Study:
- To systematically review and meta-analyze the existing literature on the association between tau proteins and MDD.
- To determine if tau protein levels or neurofibrillary tangles are altered in individuals with MDD.
Main Methods:
- Systematic literature review of 49 articles.
- Meta-analysis of cerebrospinal fluid (CSF) total and phosphorylated tau levels in MDD vs. controls.
- Analysis of positron emission tomography (PET) and clinicopathological studies.
Main Results:
- No significant differences were found in CSF total or phosphorylated tau levels between MDD patients and controls.
- Subgroup analysis excluding studies with significant age differences yielded similar results.
- PET studies lacked specificity, and clinicopathological studies did not associate neurofibrillary tangles with MDD.
Conclusions:
- The current body of evidence does not support a direct link between tau pathology and MDD.
- Data on tau in MDD is limited, and its involvement in a subset of MDD cases warrants further prospective investigation.
