ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Amyloid Pathology Modulates the Relationship Between Subsyndromal Symptomatic Depression and Tau Accumulation in Non-Demented Older Adults
Provisionally accepted
- 1Heze hospital affiliated of Shandong first medical university, Heze, China
- 2Shandong First Medical University, Jinan, China
- 3Yantai Yuhuangding Hospital, Yantai, China
- 4Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai, China
- 5Jiaozhou Hospital of Tongji University Dongfang Hospital, Jiaozhou, China
- 6Yantaishan Hospital - North Campus, Yantai, China
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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 two 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 accumulation 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.
Keywords: Subsyndromal symptomatic depression, amyloid-β, tau, Alzheimer's disease, Neuroimaging Biomarkers
Received: 04 Aug 2025; Accepted: 24 Nov 2025.
Copyright: © 2025 Bai, Wei, Wei, Tai, Kong, Ba and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Min Kong
Maowen Ba
Chunhua Zhang
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