Sporadic four-repeat tauopathy with frontotemporal lobar degeneration, Parkinsonism, and motor neuron disease: a distinct clinicopathological and biochemical disease entity.
Tau is the pathological protein in several neurodegenerative disorders classified as frontotemporal lobar degeneration (FTLD), including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). We report an unusual tauopathy in three Japanese patients presenting with Parkinsonism and motor neuron disease (neuroimaging revealed frontotemporal cerebral atrophy in two patients who were examined). At autopsy, all cases showed FTLD with the most severe neuronal loss and gliosis evident in the premotor and precentral gyri. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. In the spinal cord, loss of anterior horn cells and degeneration of the corticospinal tract were evident. In addition, the affected regions exhibited neuronal cytoplasmic inclusions resembling neurofibrillary tangles. Immunostaining using antibodies against hyperphosphorylated tau and 4-repeat tau revealed widespread occurrence of neuronal and glial cytoplasmic inclusions in the central nervous system; the astrocytic tau lesions were unique, and different in morphology from astrocytic plaques in CBD, or tufted astrocytes in PSP. However, immunoblotting of frozen brain samples available in two cases revealed predominantly 4R tau, with the approximately 37-kDa and 33-kDa low-molecular mass tau fragments characteristic of CBD and PSP, respectively. No mutations were found in the tau gene in either of the two cases. Based on these clinicopathological, biochemical, and genetic findings, we consider that the present three patients form a distinct 4R tauopathy associated with sporadic FTLD.
Department of Pathology, Brain Research Institute, University of Niigata, Chuo-ku, Japan.
Yong-Juan
YJ
Fu
Yasushi
Y
Nishihira
Shigetoshi
S
Kuroda
Yasuko
Y
Toyoshima
Tomohiko
T
Ishihara
Makoto
M
Shinozaki
Akinori
A
Miyashita
Yue-Shan
YS
Piao
Chun-Feng
CF
Tan
Takashi
T
Tani
Ryoko
R
Koike
Keisuke
K
Iwanaga
Mitsuhiro
M
Tsujihata
Osamu
O
Onodera
Ryozo
R
Kuwano
Masatoyo
M
Nishizawa
Akiyoshi
A
Kakita
Takeshi
T
Ikeuchi
Hitoshi
H
Takahashi
D000328:Adult; D000368:Aged; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D057174:Frontotemporal Lobar Degeneration / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D020734:Parkinsonian Disorders / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D024801:Tauopathies / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
C054369:MAPT protein, human; D016875:tau Proteins