ABSTRACT
Frontotemporal lobar degeneration (FTLD) is characterized by a variety of behavioral and psychiatric symptoms based on the dysfunction of frontal and/or temporal lobes. A 63-year-old Japanese man without a family history of neurological diseases developed progressive symptoms of frontotemporal dementia, followed by motor neuron disease (MND). Brain magnetic resonance images demonstrated severe atrophy in the anterior temporal lobes from early clinical stage. The symptoms got rapidly worsened and the patient died of respiratory failure 1year 8months after the disease onset. A postmortem study revealed severe and circumscribed atrophy in the anterior temporal lobes, and histological examination disclosed marked neuronal loss with many neuronal cytoplasmic inclusions which were immunoreactive for ubiquitin antibodies and phosphorylated TAR DNA-binding protein of 43kDa (TDP-43) antibodies in hippocampal dentate granule cells and amygdalae, as well as a few neuronal cytoplasmic inclusions without dystrophic neurites in the temporal neocortex. This case report showed typical features of FTLD-MND in clinical course and TDP-43 pathology with unusual severity and distribution of cerebral atrophy, suggesting a unique manifestation of FTLD-MND.
Subject(s)
Frontotemporal Lobar Degeneration/complications , Motor Neuron Disease/complications , Temporal Lobe/pathology , Asian People , Atrophy , DNA-Binding Proteins/metabolism , Humans , Magnetic Resonance Imaging/methods , Male , Melanins/metabolism , Middle Aged , Ubiquitin/metabolismABSTRACT
Increasing evidence suggests that alpha-synuclein is a common pathogenic molecule in several neurodegenerative diseases, particularly in Parkinson's disease. To understand alpha-synuclein pathology, we investigated molecules that interact with alpha-synuclein in human and rat brains and identified tubulin as an alpha-synuclein binding/associated protein. Tubulin co-localized with alpha-synuclein in Lewy bodies and other alpha-synuclein-positive pathological structures. Tubulin initiated and promoted alpha-synuclein fibril formation under physiological conditions in vitro. These findings suggest that an interaction between tubulin and alpha-synuclein might accelerate alpha-synuclein aggregation in diseased brains, leading to the formation of Lewy bodies.
