Revisiting the utility of TDP-43 immunoreactive (TDP-43-ir) pathology to classify FTLD-TDP subtypes
Until 2006, the term “frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U)” referred to a classification system with subtypes based on the distribution of neuronal cytoplasmic inclusions (NCIs), dystrophic neurites (DNs), and neuronal intranuclear inclusions (NIIs), which were immunoreactive to ubiquitin, and tau- and alpha-synuclein negative . In 2006, the 43-kDa TAR DNA-binding protein (TDP-43) was identified as the elemental ubiquitinated protein in FTLD-U, and soon thereafter, the harmonized classification of FTLD-TDP was derived, giving rise to four subtypes (A, B, C, and D) [3, 4]. The term “FTLD-U” was thus replaced with “FTLD-TDP” because cases positive for TDP-43 could be identified based on TDP-43 immunoreactivity (TDP-43-ir). The most obvious challenge to the present FTLD-TDP-based vs. the past FTLD-U-based classification system is that immunohistochemistry for TDP-43 identifies pathologic patterns that are somewhat different from immunohistochemistry...