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Younkin, Steven G

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Ubiquitin immunohistochemistry of frontotemporal lobar degeneration differentiates cases with and without motor neuron disease.

Omi Katsuse; Dennis W Dickson (Profiled Author: Dickson, Dennis)

Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
Alzheimer disease and associated disorders 2005;19 Suppl 1():S37-43.

Abstract

Frontotemporal lobar degeneration (FTLD) without tau pathology is clinically and pathologically heterogeneous. The present report describes the neuropathology of 52 brains with FTLD without tau pathology compared with 10 brains of amyotrophic lateral sclerosis (ALS) without dementia using ubiquitin immunohistochemistry. The 52 cases were classified into 47 cases of FTLD with motor neuron disease (MND)-type inclusions but without MND (FTLD-MNI), three cases of FTLD with MND (FTLD-MND), and two cases of dementia lacking distinctive histopathology (DLDH) based on the features of ubiquitin-immunoreactive (ubiquitin-ir) structures in the caudate, frontotemporal cortices and dentate fascia, and presence or absence of neuronal loss in lower motor neurons. Many ubiquitin-ir neuronal inclusions and neurites in the caudate nucleus, frontotemporal cortices, and ubiquitin-ir crescent-or ring-shaped neuronal inclusions in the dentate fascia characterized FTLD-MNI. Ubiquitin-ir neuronal intranuclear inclusions (NII) were observed in 26 of 43 cases and associated with many neurites in the caudate nucleus as well as a familial history in most cases. A subset of cases had Pick-body-like inclusions in the dentate fascia and caudate nucleus with paucity of neuritic pathology and no NII; another had crescent-shaped inclusions in the dentate fascia and neuritic pathology with NII in the caudate. FTLD with MND was characterized by a few or no ubiquitin-ir inclusions in the caudate nucleus and frontotemporal cortices and ubiquitin-ir granular inclusions in the dentate fascia, as well as loss of lower motor neurons. These features were similar to ALS, but different from FTLD-MNI. The findings suggest that FTLD-MNI has a different pathogenesis from FTLD-MND and ALS.

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