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Acta Neuropathol (1994) 88:207-211 ?9 Springer-Verlag 1994 Y. Yoshiyama ?9 T. Yamada ?9 K. Asanuma ?9 T. Asahi Apoptosis related antigen, Le Y and nick-end labeling are positive in spinal motor neurons in amyotrophic lateral sclerosis Received: 2 February 1994 / Revised, accepted: 15 March 1994 Abstract Expression of Le v, a difucosylated type 2 chain determinant, has been previously identified as a characteristic of cells undergoing apoptosis. Immuno- histochemistry using an antibody for Le~ as well as nick-end labeling for the detection of DNA breaks, was done on cervical spinal cord sections from ten patients with amyotrophic lateral sclerosis (ALS) and nine pa- tients who had died from other causes. LeV-positive immunoreactivity was seen in the motor neurons of seven ALS cases, but in none of the other cases. Nick- end labeling was also positive in four ALS cases. Dou- ble staining of motor neurons by anti-Le v antibody and nick-end labeling was shwon in these cases. Other Le v- positive structures, such as reactive astrocytes and fat- laden microgtia/macrophages in the lateral and anterior columns, were negative for nick-end labeling. These results suggest that the mechanism of cell death in the spinal motor neurons of ALS may be apoptosis. Key words Amyotrophic lateral sclerosis ?9 Le Y Nick-end labeling ?9 Apoptosis introduction Affected motor neurons in amyotrophic lateral sclerosis (ALS) display atrophy and surviving neurons some- times have cytoplasmic inclusions, such as hyaline inclusions, Bunina bodies and/or skein-like inclusions. Supported by grants from the Ministry of Education in Japan Y. Yoshiyama [] ?9 T. Yamada Department of Neurology, School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260, Japan K. Asanuma Department of Pathology, Matsudo Municipal Hospital, Matsudo, Japan T. Asahi Asahi Hospital, Matsudo, Japan A recent study by Kiernan et al. [11] showed decreases in size and changes in shape of some of the remaining motor neurons in ALS spinal cord and suggested the mechanism of neuronal atrophy might involve reduced protein synthesis and enzymatic degradation of the cytoskeleton within the larger dendrites. Another recent work by Mourelatos et al. [13] demonstrated that fragmented Golgi apparatus were frequent in ALS motor neurons, suggesting this was an early change, probably related to the pathogenesis of the neuronal death. Classification of cell death is based on morphological or biochemical criteria or on the circumstances under which it occurs. One mode of death has been named apoptosis [9], or programmed cell death. This is a basic biological process, apparently occurring in both physio- logical or pathological processes. Cell death by apop- totic process has been suspected in prion-related ence- pahlopathy [4] and Alzheimer's disease [5]. Using an antibody to Le Y, a difucosylated type 2 chain deter- minant (Fucct 1-->2Galgl--~4[Fuccd-~3] GlcNAcI31-R), changes in specific glycosylation patterns have been cor- related with apoptosis in various human tissues [8]. Le v has been identified in apoptotic cells of both normal and tumor tissues [8]. Nick-end labeling, to detect DNA fragmentation, is a second technique which has been used [2, 6, 7] to detect cells undergoing apoptosis. We have used both techniques in a study of spinal cord sections from cases of ALS as compared with neurologi- cal and non-neurological (NND) controls; a number of the ALS cases were the only ones studied to yield evi- dence of apoptosis of motor neurons. Materials and methods Ten ALS, four progressive supranuclear palsy (PSP), one lacunar stroke, one polyarteritis nodosa (PN) and three NND cases were examined in this study. Data on the sex, age and disease duration for each case are given in Table 1. The clinical diagnosis of ALS was based on the presence of both upper and lower motor neuron symptoms and signs, with or without bulbar signs, and with a pro-