In vivo biomarkers for limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC): A scoping review of proposed measures

BackgroundLimbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a common cause of late-life amnestic dementia that mimics Alzheimer's disease but lacks a validated in vivo biomarker.ObjectiveThe authors sought to map the in vivo biomarker candidates for LATE-NC, characterize the type and quality of evidence for each, highlight their validation against postmortem TDP-43 staging and map their performance in both pure LATE-NC and mixed pathology.MethodsFive databases were searched (PubMed/MEDLINE, EMBASE, Web of Science, Cochrane Library, Scopus). Eligible studies investigated in vivo biomarkers for LATE-NC in adults with mean age above 65. Two reviewers independently screened all records; a third adjudicated disagreements. Data were extracted across 24 fields and synthesized narratively.Results43 studies covering structural MRI (19), FDG-PET (8), plasma (7), diffusion MRI (4), multimodal MRI (1), CSF (2), TDP-43 PET (1), and linguistic markers (1) were reviewed. The most replicated signal was medial temporal lobe atrophy and hypometabolism. Several studies framed their candidate as a diagnostic validation against autopsy; yet only three reported formal performance metrics with stated cut-off values. A handful of studies (12%) tested in an independent cohort and the corpus contains only one study from outside North America and Europe (Japan).ConclusionsImaging evidence is well-anchored but mostly exploratory or surrogate validated at this stage. Plasma TDP-43 elevation is consistent but no commercial assay has a validated cut-point. Clinical translation requires external validation, cut-point-anchored diagnostic accuracy, and cohort diversification.