Ubiquitinated neuronal inclusions in the neostriatum in patients with amyotrophic lateral sclerosis with and without dementia--a study of 60 patients 31 to 87 years of age.
OBJECTIVE
Neuronal degeneration in amyotrophic lateral sclerosis (ALS) is associated with ubiquitinated cytoskeletal alterations in the motor neuron system. Ubiquitin-positive inclusions are also seen in the limbic system in ALS with dementia (ALS-D). Recently, similar inclusions were reported to occur in the neostriatum in a case of ALS-D. We, therefore, immunohistochemically examined the neostriatum from 60 patients with ALS and 60 control subjects.


RESULTS
Two forms of ubiquitin-positive inclusions were found in the ALS neostriatum: rod-like inclusions in the large neurons and crescent-shaped inclusions in the small neurons. The former were found in 14 ALS and 18 control subjects, whereas the latter were specific to ALS; the crescent-shaped inclusions in small neurons were found in 27 ALS patients, and the immunohistochemical and ultrastructural features were identical to those of the extra-motor inclusions of ALS. Moreover, characteristic temporal lesions consistent with those seen in ALS-D were found in 8 patients, of whom 2 had shown dementia.


CONCLUSIONS
The present findings strongly suggest that neostriatal small neurons are also involved in the disease process in ALS.
Wakabayashi
K
K
Brain Disease Research Center, Niigata University, Japan. koichi@cc.hirosaki-u.ac.jp
Piao
Y S
YS
Hayashi
S
S
Kakita
A
A
Yamada
M
M
Takahashi
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003704:Dementia / Q000473:pathology*; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology*; D008032:Limbic System / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000473:pathology*; D009046:Motor Neurons / Q000473:pathology; D019579:Neocortex / Q000473:pathology*; D009474:Neurons / Q000473:pathology