Immunohistochemical and ultrastructural characterization of ubiquitinated eosinophilic fibrillary neuronal inclusions in sporadic amyotrophic lateral sclerosis.
We found eosinophilic fibrillary neuronal inclusions (EFNI) that were argyrophilic and immunoreactive for anti-ubiquitin in the cerebral cortex of a patient with sporadic amyotrophic lateral sclerosis (ALS) and mild personality changes. Both hematoxylin and eosin and Bodian's preparations revealed the EFNI to be rod-, flame-shaped, or spherical structures existing within the swollen neuronal perinuclear region in the third, fifth, and sixth layers of the fronto-parieto-temporal cortices including the primary motor cortex. On electron microscopy, filamentous profiles aggregated and formed a single bundle or globule in the neuronal perikaryon without any limiting membrane. Most EFNI had a characteristic multiple layer arrangement. The inner core consisted of randomly oriented granule-free tubules with a fuzzy outer contour, measuring 15-20 nm in diameter. The surrounding layer was made up of granule-associated filaments, electrondense free granules, and small vesicular profiles. Large autolysosome-like membrane-bound vesicular profiles were found scattered at the periphery. Neurofilaments were usually mingled with in the surrounding cytoplasm. Many EFNI were also found in dendrites, but only a few in axons. Both granule-free tubules and granule-associated filaments expressed ubiquitin protein epitopes. Aberrant phosphorylation of neurofilament protein and induction of alphaB-crystallin were shown to exist in EFNI-bearing swollen neurons. Despite having a variety of histological appearances, our observations revealed that EFNI all have common immunocytochemical and ultrastructural characteristics, and thus we assume that EFNI represent a series of cytological alterations in the motor and extra-motor cortices of ALS patients.
Arima
K
K
Department of Ultrastructure and Histochemistry, Tokyo Institute of Psychiatry, Japan. arima@prit.go.jp
Ogawa
M
M
Sunohara
N
N
Nishio
T
T
Shimomura
Y
Y
Hirai
S
S
Eto
K
K
D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology*; D001344:Autopsy; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000502:physiology; D003459:Crystallins / Q000378:metabolism; D004804:Eosinophils / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure*; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology; D009454:Neurofibrils / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure*; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure*; D014452:Ubiquitins / Q000378:metabolism*
D003459:Crystallins; D014452:Ubiquitins