Neuropathological heterogeneity in frontotemporal lobar degeneration with TDP-43 proteinopathy: a quantitative study of 94 cases using principal components analysis

摘要: Studies suggest that frontotemporal lobar degeneration with transactive response DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP) is heterogeneous division into four or five subtypes. To determine the degree heterogeneity and validity subtypes, we studied neuropathological variation within frontal temporal lobes 94 cases FTLD-TDP using quantitative estimates density principal components analysis (PCA). A PCA based on TDP-43 immunoreactive neuronal cytoplasmic inclusions, oligodendroglial intranuclear dystrophic neurites, surviving neurons, enlarged vacuolation suggested were not segregated distinct Variation in vacuoles was greatest source between cases. pathology alone progranulin (GRN) mutation to some degree. The pathological phenotype all subtypes overlapped but 1 4 most distinctive. Cases coexisting motor neuron disease (MND) hippocampal sclerosis (HS) also appeared segregate extent. We suggest: (1) best described as a ‘continuum’ without clearly (2) single reflects ‘stage’ disease, (3) GRN MND HS may have more distinctive pathology.