Limbic-Predominant Age-Related TDP-43 Encephalopathy: LATE-Breaking Updates in Clinicopathologic Features and...

Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently defined neurodegenerative disease characterized by amnestic phenotype and pathological inclusions of TAR DNA-binding protein 43 (TDP-43). LATE is distinct from rarer forms of TDP-43 diseases such as frontotemporal lobar degeneration with TDP-43 but is also a common copathology with Alzheimer's disease (AD) and cerebrovascular disease and accelerates cognitive decline. LATE contributes to clinicopathologic heterogeneity in neurodegenerative diseases, so it is imperative to distinguish LATE from other etiologies.

Novel biomarkers for LATE are being developed with magnetic resonance imaging (MRI) and positron emission tomography (PET). When cooccurring with AD, LATE exhibits identifiable patterns of limbic-predominant atrophy on MRI and hypometabolism on ¹⁸F-fluorodeoxyglucose PET that are greater than expected relative to levels of local AD pathology. Efforts are being made to develop TDP-43-specific radiotracers, molecularly specific biofluid measures, and genomic predictors of TDP-43. LATE is a highly prevalent neurodegenerative disease distinct from previously characterized cognitive disorders.