Limbic neurodegenerative disease: How radiologists can identify a common but underdiagnosed cause of dementia

Limbic-predominant Age-related TDP-43 Encephalopathy (LATE) is a pathology-based diagnosis which represents an increasingly recognized but substantially underappreciated cause of dementia in older adults, potentially accounting for 15-25% of cases clinically diagnosed as Alzheimer's Disease. Limbic-predominant Amnestic Neurodegenerative Syndrome (LANS) is an overlapping proposed clinical diagnosis based on functional patterns of limbic-predominant neurodegeneration. This educational review examines the pathologic basis, clinical presentation, and multimodal imaging features of LATE and LANS, with emphasis on the role of radiology in the diagnostic algorithm. Both entities are characterized by relatively late presentation and an indolent course of progressive memory loss. Two diagnostic frameworks are presented: the NIA-AA ATN-based approach utilizing amyloid and tau biomarkers to establish "probable" or "possible" LATE diagnoses, and the Mayo Clinic LANS framework emphasizing functional neuroimaging to elucidate patterns of neurodegeneration. As targeted therapies improve, more accurate diagnosis is becoming increasingly important for appropriate patient selection, prognostic counseling, and future targeted therapeutic trials. Radiologists play an essential role in recognizing the characteristic imaging phenotype and raising clinical awareness of LATE and LANS.