Preprint · Jan 2026
In vivo detection of limbic-predominant age-related TDP-43 encephalopathy (LATE-NC): a scoping review of proposed biomarkers and their neuropathological validation
By Reuben S, Adeleye AS, Singh R et al.
This is a prospectively registered scoping review protocol, uploaded prior to commencement of database searches. Review team: Ravi Singh, Soala Reuben, Mathew Oyelami, Adesola Adeleye, Department of Pathology, St. George's University Methodology: Conducted following Arksey and O'Malley (2005) as refined by Levac et al. (2010); reported in accordance with PRISMA-ScR (Tricco et al., 2018) Review question: What in vivo biomarkers, including neuroimaging, cerebrospinal fluid, and plasma-based markers, have been proposed or evaluated for the detection of limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) in older adults, and what is the current evidence for their performance against post-mortem neuropathological confirmation as ground truth? Background: LATE-NC affects an estimated 20 to 40 per cent of individuals aged 85 and older and is a common co-pathology with Alzheimer's disease neuropathological change. Despite its clinical significance, no widely accepted molecularly specific in vivo biomarker for TDP-43 pathology currently exists. This review will systematically map the landscape of proposed biomarker candidates and evaluate the evidence for their neuropathological validation. Databases to be searched: PubMed/MEDLINE, EMBASE, Web of Science (Core Collection, KCI-Korean Journal Database, ProQuest Dissertations and Theses Citation Index, SciELO Citation Index, and Preprint Citation Index), Cochrane Library, and Scopus. Current stage: Protocol complete. Registered prior to commencement of database searches. Full protocol: See attached document for complete methodology including PEO framework, eligibility criteria, full search strings, screening procedures, and data charting plan.