title: Sporadic four-repeat tauopathy with frontotemporal degeneration, parkinsonism and motor neuron disease.
abstract: We report a sporadic tauopathy of 6-year duration in a 76-year-old woman. Her initial symptoms were asymmetrical parkinsonism and muscle weakness, with apraxia appearing 2 years later. The brain showed frontal and temporal cerebral atrophy; severe neuronal loss and gliosis were observed in the precentral cortex (loss of Betz cells was also evident) and premotor area, and in the medial temporal lobe, including the temporal tip, amygdala, and hippocampal CA1-subiculum border zone. The substantia nigra showed moderate neuronal loss and gliosis. In the spinal cord, loss of the anterior horn cells and degeneration of the corticospinal tracts were a characteristic feature. In addition, in the affected regions, the remaining neurons were often found to contain intracytoplasmic inclusions resembling neurofibrillary tangles. Tau immunostaining revealed widespread glial-predominant lesions in the cerebral gray and white matter. In contrast, predominance of neuronal lesions (pretangles/tangles) was a feature in the subcortical gray matter, including the spinal cord. The remaining upper and lower motor neurons were also affected by tau pathology. Accumulated tau in these glial cells and neurons was clearly recognized by a specific antibody against four-repeat (4R) tau. The ultrastructural presence of tau-positive tubular structures was confirmed in the glial cells and neurons (tangles). Immunoblotting of a frozen frontal lobe sample revealed accumulation of 4R-predominant tau isoforms. No mutations were found in the tau gene. These findings indicate that a sporadic 4R tauopathy can cause frontotemporal degeneration, parkinsonism, and motor neuron disease. The present case could represent a new clinicopathological phenotype of non-familial tauopathy.
authors.affiliation: Department of Pathology, Brain Research Institute, University of Niigata, 1-757 Asahimachi, 951-8585, Niigata, Japan.
authors.forename: Yue-Shan
authors.initials: YS
authors.lastname: Piao
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Tan
authors.forename: Keisuke
authors.initials: K
authors.lastname: Iwanaga
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takano
authors.forename: Masatoyo
authors.initials: M
authors.lastname: Nishizawa
authors.forename: Tammaryn
authors.initials: T
authors.lastname: Lashley
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
authors.forename: Andrew
authors.initials: A
authors.lastname: Lees
authors.forename: Rohan
authors.initials: R
authors.lastname: de Silva
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Tsujihata
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000368:Aged; D001253:Astrocytes / Q000473:pathology; D003704:Dementia / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D016253:Microscopy, Immunoelectron; D016472:Motor Neuron Disease / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D009474:Neurons / Q000473:pathology; D020734:Parkinsonian Disorders / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D013116:Spinal Cord / Q000473:pathology; D024801:Tauopathies / Q000150:complications / Q000473:pathology* / Q000503:physiopathology