Senile onset frontotemporal lobar degeneration with TAR‐DNA binding protein 43 proteinopathy primarily presenting with wasteful habits

Abstract

We present an autopsied case of a senile Japanese woman with sporadic frontotemporal lobar degeneration (FTLD) presenting as frontotemporal dementia. Disease onset was at the age of 70 and presented as a behaviour disorder, particularly involving wasteful habits. The patient had repeated incidents of making expensive purchases and then had difficulty making payments. Following these symptoms, she showed other changes of character such as lethargy and apathy. She gradually showed signs of parkinsonism including rigidity and bradykinesia, and in the terminal stage, an akinetic mutism state with quadriplegia in flexion was observed. Head magnetic resonance imaging revealed severe frontotemporal lobe atrophy with severe lateral ventricular dilatation and frontal white matter degeneration. At autopsy, the brain weighed 930 g and the frontotemporal cerebral cortex showed neuron loss with gliosis, tissue rarefaction and spongiform change, particularly in the superficial layers. Pathologic degeneration was more severe in the anterior portion of the frontal lobe with extensive white matter degeneration. Immunostaining for phosphorylated TAR-DNA binding protein 43 (TDP-43) revealed numerous neuronal cytoplasmic inclusions and extensive short dystrophic neuritis, particularly in the frontotemporal cortex. Many TDP-43-positive cytoplasmic inclusions were also observed in the dentate gyrus of the hippocampus. The patient was pathologically diagnosed with FTLD with TDP-43-positive inclusions (FTLD-TDP) without motor neuron disease. The immunohistochemical findings corresponded to type A of the FTLD-TDP pathology classification system.