PET-measured tau deposition in emotion-related brain regions is differentially associated with depressive symptoms in individuals with versus without Alzheimer's disease pathology.
Academic Article
Overview
abstract
Depressive symptoms are common in patients diagnosed with Alzheimer's Disease (AD) and can also precede AD as a risk factor and/or prodrome. Brain deposition of hyper-phosphorylated tau is a hallmark pathology of AD. Tau deposition in brain regions involved in emotional processing is likely to be pathophysiologically relevant to these links between AD and depression. We used 18F-MK6240 PET to measure tau in amygdala, hippocampus, and nucleus accumbens-regions implicated in depression-in 141 participants with and without AD. In addition to tau PET, participants underwent amyloid-beta (Aβ) PET, MRI, and cognitive evaluation. Depressive symptoms were assessed with the Beck Depression Inventory (BDI). Multiple regression analyzed contributions of tau and Aβ status (positive vs. negative), depression (BDI > 13), cognition (impaired vs. normal), age and sex to tau burden in the three regions. A significant interaction between tau status and depression prompted subgroup analyses of tau-positive (n=34) and tau-negative (n=107) participants. Among tau-positive participants, depression was associated with greater tau in the nucleus accumbens, a region critical for reward processing and motivation. This finding suggests that tau-mediated accumbens dysfunction may contribute to anhedonia, a key symptom of depression that is particularly common in AD-related depression. In tau-negative participants, greater depression was associated with less tau in the medial temporal lobe. This unexpected finding requires confirmation through further research, but could reflect impaired neurogenesis in depression without AD pathology.
