title: Ubiquitin immunohistochemistry suggests classic motor neuron disease, motor neuron disease with dementia, and frontotemporal dementia of the motor neuron disease type represent a clinicopathologic spectrum.
abstract: One of the characteristic pathologic changes in classic motor neuron disease (MND) is the presence of ubiquitin-immunoreactive (ub-ir) inclusions in the cytoplasm of lower motor neurons. In addition, cases of MND with dementia (MND-d) also have ub-ir neuronal cytoplasmic inclusions and dystrophic neurites in extramotor neocortex and hippocampus. Although this extramotor pathology is a highly sensitive marker for dementia in MND, similar changes are found in a subset of patients with frontotemporal dementia (FTD) with no motor symptoms (FTD-MND type). The purpose of this study is to more fully describe and compare the pattern of ub-ir pathology in these 3 conditions. We performed ubiquitin immunohistochemistry on postmortem tissue, representing a wide range of neuroanatomic structures, in cases of classic MND (n = 20), MND-d (n = 15), and FTD-MND type (n = 15). We found the variety of morphologies and the anatomic distribution of ub-ir pathology to be greater than previously documented. Moreover, the degree of overlap suggests that MND, MND-d, and FTD-MND type represent a spectrum of clinical disease with a common pathologic substrate. The only finding restricted to a specific subgroup of patients was the presence of ub-ir neuronal intranuclear inclusions in some cases of familial FTD.
authors.affiliation: Division of Neuropathology, University of British Columbia, Vancouver, Canada. ian.mackenzie@vch.ca
authors.forename: Ian R A
authors.initials: IR
authors.lastname: Mackenzie
authors.forename: Howard H
authors.initials: HH
authors.lastname: Feldman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003704:Dementia / Q000145:classification / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D009410:Nerve Degeneration / Q000150:complications / Q000378:metabolism / Q000473:pathology; D016501:Neurites / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011180:Postmortem Changes; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D025801:Ubiquitin