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Amyloid pathology modulates the relationship between subsyndromal symptomatic depression and tau accumulation in non-demented older adults

Jiahe Bai,Xiaonan Wei,Hongchun Wei,Yaojun Tai,Min Kong,Maowen Ba,Chunhua Zhang

Published 2025 in Frontiers in Aging Neuroscience

ABSTRACT

Objective Subsyndromal symptomatic depression (SSD) has been increasingly implicated in the pathophysiological processes of Alzheimer’s disease (AD). However, it remains unclear whether SSD and amyloid-β (Aβ) pathology jointly contribute to tau deposition. This study aimed to investigate the interaction between SSD and Aβ status on regional tau accumulation in non-demented older adults. Materials and methods We analyzed data from 391 non-demented older adults in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) who underwent Aβ and tau positron emission tomography (PET) scans, as well as Geriatric Depression Scale (GDS-15) assessments. Aβ positivity (Aβ+) was defined by established tracer-specific standardized uptake value ratio (SUVR) thresholds (≥1.11 for 18F-florbetapir or ≥1.08 for 18F-florbetaben). SSD was defined as a GDS-15 score of 1–5. Linear mixed-effects models were applied to assess the longitudinal effects of SSD and Aβ status on regional tau accumulation over 2 years. Results At baseline, significant interactions between SSD and Aβ status were observed for regional tau SUVRs, with the Aβ+/SSD+ group exhibiting significantly higher tau levels across all Braak stages compared with the other groups. Longitudinal analyses identified a significant three-way interaction among SSD, Aβ status, and time in the Braak III/IV and Braak V/VI regions. Moreover, the Aβ+/SSD+ group demonstrated significantly faster tau accumulation compared to all other groups. The Aβ+/SSD− group also exhibited greater tau accumulation than the Aβ−/SSD− group, whereas no significant differences were observed between the Aβ− groups. Conclusion These findings suggest that SSD is associated with greater early tau accumulation in individuals with Aβ pathology.

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