Dual pathologies: Utility of TAR DNA‐binding Protein 43 (TDP‐43) Staining in Patients with Frontal and Temporal Lobe Abnormalities and Alzheimer disease

Abstract

Prominent behavioral changes and language dysfunction are features of frontotemporal lobar degeneration (FTLD) but can also occur in AD. Recently, application of TAR DNA-binding protein 43 (TDP-43) antibody has been shown to be useful for demonstrating the pathologic lesions of FTLD-U and FTLD-MND. Since these cases might represent combined disorders (FTD and AD), we studied the utility of TDP-43 staining to demonstrate inclusion bodies in brains of patients with clinical features of frontal or temporal lobe dysfunction but with autopsy features of AD. METHODS: Eight patients from 1998 to 2005 were identified, including 1 with combined pathologic features of FTLD-U (previously identified with anti-ubiquitin staining) and mild AD (Braak stage IV). Sections of hippocampus and frontal and temporal lobes were stained with anti-TDP-43 antibody (Proteintech Group). RESULTS: Of the 8 patients, 1 had advanced AD (Braak stage VI) and scattered TDP-43 positive cytoplasmic inclusions in hippocampal dentate granular cells and frontal and temporal neocortical neurons. The previously identified patient with combined FTLD-U and mild AD also had TDP-43 positive cytoplasmic and nuclear inclusions. CONCLUSION: TDP-43 aids in the identification of case with dual pathologies, particularly in advanced AD where inclusion may be masked by overwhelming AD pathology.