Ubiquitin and TDP‐43 immunohistochemistry: how many types of frontotemporal lobar degeneration?

Abstract

Objective: Frontotemporal lobar degeneration with ubiquitin (Ub)‐immunoreactive (ir) inclusions (FTLD‐U) has been classified into four different pathological subtypes. Aim of this study is to assess the applicability of this classification to our series of FTLD‐U cases. Methods: Ub and TDP‐43‐immunohistochemistry (IHC) were carried out on tissue from 53 cases with pathological diagnosis of FTLD‐U, ALS or dementia lacking distinctive histopathology (DLDH). Results: 25 cases were classified according to the proposed criteria (type I: 5; Type II: 7; type III: 9; type IV: 4). Among the other 28 cases, we identified 6 distinct groups: a) ALS with Ub and TDP‐43 pathology confined to the motor neurons only (5); b) ALS with Ub‐ir/TDP‐43‐negative inclusions (4); c) FTD with Ub‐ir and TDP‐43‐ir inclusions limited to the dentate gyrus (DG) (4); d) FTD with Ub‐ir and TDP‐43‐negative inclusions limited to the DG (4); e) FTD with FTLD‐U type II‐like pathology with Ub‐ir/TDP‐43‐negative inclusions (2); f) DLDH (9). Conclusions: The use of Ub and TDP‐43 IHC allowed the classification of 47.1% of cases from our series, according to the criteria. 17% had a pathological diagnosis of DLDH. Among those cases not meeting criteria for inclusion in one of the proposed subtypes, new possible subtypes, potentially associated with novel biological mechanisms of neurodegeneration were observed. Supported by AG10133