Biomarker profiles in late-life depression and Alzheimer's disease across and beyond the A/T/N framework: A scoping review.

Depression and Alzheimer's disease (AD) frequently overlap clinically, and depressive symptoms may signal major depressive disorder, a risk factor for AD, or an early manifestation of neurodegeneration. This scoping review mapped biomarker evidence differentiating depression and AD within and beyond the amyloid/tau/neurodegeneration (A/T/N) framework. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines, MEDLINE, Embase, and Scopus were searched for studies published between 2010 and 2025 examining biomarkers in depression and AD. Eligible studies included clinical diagnoses of AD and/or depression and reported biomarker measures. Forty-eight studies met inclusion criteria. Amyloid biomarkers were most consistently associated with clinically diagnosed AD, whereas findings for other biomarkers were more heterogeneous. Neurodegeneration markers, including hippocampal atrophy, were commonly associated with AD, while vascular abnormalities and altered functional connectivity were more frequently linked to depressive symptoms. Overall, AD and depression demonstrated partially distinct but overlapping biomarker profiles, highlighting the need for longitudinal studies using scalable biomarkers to clarify causal and temporal relationships.