TDP-43 Pathologic Lesions and Clinical Phenotype in Frontotemporal Lobar Degeneration With Ubiquitin-Positive Inclusions

Abstract

Frontotemporal dementia (FTD) is a progressive neurodegenerative disease manifesting as language dysfunction or as a disorder of social comportment and executive functioning.^1,2 This condition is as common as Alzheimer disease in individuals younger than 65 years.^3-5 The single most common histopathological diagnosis associated with FTD is frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U),^6-8 characterized by ubiquitin-positive and tau-negative and α-synuclein–negative inclusions. Similar pathologic inclusions are seen in motor neuron disease (MND), a neurodegenerative disease affecting motor neurons in which a disorder of social, executive, or language functioning may co-occur in up to half of these patients.^9,10