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The aim of this study was to improve the neuropathologic recognition and provide criteria for the pathological diagnosis in the neurodegenerative diseases grouped as frontotemporal lobar degeneration (FTLD); revised criteria are proposed. Recent advances in molecular genetics, biochemistry, and neuropathology of FTLD prompted the Midwest Consortium for(More)
Excitotoxicity has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). More recently, glial involvement has been shown to be essential for ALS-related motoneuronal death. Here, we identified an N-methyl-D-aspartate (NMDA) receptor co-agonist, D-serine (D-Ser), as a glia-derived enhancer of glutamate (Glu) toxicity to ALS motoneurons.(More)
Amyotrophic lateral sclerosis (ALS) is a late-onset, fatal disorder in which the motor neurons degenerate. The discovery of new drugs for treating ALS has been hampered by a lack of access to motor neurons from ALS patients and appropriate disease models. We generate motor neurons from induced pluripotent stem cells (iPSCs) from familial ALS patients, who(More)
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. Accumulating evidence has shown that 43kDa TAR-DNA-binding protein (TDP-43) is the disease protein in ALS and frontotemporal lobar degeneration. We previously reported a familial ALS with Bumina bodies and TDP-43-positive skein-like inclusions in the lower motor neurons; these(More)
Optineurin is a gene associated with normal tension glaucoma and primary open-angle glaucoma, one of the major causes of irreversible bilateral blindness. Recently, mutations in the gene encoding optineurin were found in patients with amyotrophic lateral sclerosis (ALS). Immunohistochemical analysis showed aggregation of optineurin in skein-like inclusions(More)
Recently, TAR DNA-binding protein of 43-kDa (TDP-43) was identified as a major component of ubiquitinated neuronal cytoplasmic inclusions observed in lower motor neurons in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions. We herein investigated the relationship between TDP-43 immunoreactivities and(More)
We report the autopsy findings of an 82-year-old woman who exhibited slowly progressive upper motor neuron signs (pseudobulbar palsy, muscle weakness and positive Babinski's sign) in the absence of lower motor neuron signs, which were followed by progressive dementia and frontotemporal atrophy, and who died 7 years and 4 months after onset of the disease.(More)
A case of frontotemporal dementia with cerebral intraneuronal ubiquitin-positive, tau- and α-synuclein-negative inclusions is reported. A 50-year-old female patient exhibited mental changes; however, no clinical evidence of motor neuron disease was detected in her 11-year history. Neuronal loss and spongiform changes were mainly found in the frontotemporal(More)
A large scale multicenter study of cerebrospinal fluid (CSF) tau levels was conducted to determine the cut-off value, sensitivity and specificity for clinical usage as a biomarker of Alzheimer's disease (AD). Its use for early and differential diagnosis and the factors that increase CSF tau levels were also examined. CSF samples from a total of 1,031(More)
Ubiquitin-positive intraneuronal inclusions were found in the extramotor cortices of ten presenile dementia patients with motor neuron disease. There were inclusions in the hippocampal granular cells and in the small neurons of the superficial layers of the temporal and frontal cortices. Bunina bodies were present in the anterior horn cells in all cases.(More)