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October 01, 1996; 47 (4 Suppl 2) Pathogenesis

Neuropathology of ALS

An overview

Asao Hirano
First published October 1, 1996, DOI: https://doi.org/10.1212/WNL.47.4_Suppl_2.63S
Asao Hirano
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Neuropathology of ALS
An overview
Asao Hirano
Neurology Oct 1996, 47 (4 Suppl 2) 63S-66S; DOI: 10.1212/WNL.47.4_Suppl_2.63S

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ALS is an age-associated neurodegenerative disease that primarily affects the motor neuron system. Despite having been studied for over 100 years, its etiology is still a mystery, and no specific diagnostic laboratory test has been developed. The diagnosis of ALS is therefore based on clinical features and/or neuropathologic findings. The neuropathologic findings on patients with classic ALS are quite distinct, with loss and degeneration of the large anterior horn cells of the spinal cord and lower cranial motor nuclei of the brainstem. The striated muscles display denervation atrophy. Upper motor neurons, such as the Betz cells in the motor cortex, are also affected. The several symposia and workshops on the cytopathology of ALS held within the past 3 years are a reflection of the many new and important developments taking place in this area. [1] Although loss of motor neurons has been known for many years, cytoplasmic alterations of the lower motor neurons have been studied in detail only in recent years by using immunohistochemical and electron microscopic techniques.

An overview of some of the novel findings associated with lower motor neuron alterations is presented here.

Synaptophysin.

The synapse is the most important site of neuronal function and is unique to the neuron. Despite many years of extensive studies on ALS, data regarding synaptic alterations are limited to a relatively small number of ultrastructural investigations. [2] This paucity of information is due to the inherent difficulties that affect the proper evaluation of synapses in autopsy material.

Synaptophysin, a 38-kDa glycoprotein, is a constituent of the membrane of synaptic vesicles in presynaptic terminals. The evaluation of synaptophysin expression in the lumbar spinal cord of ALS patients was apparently presented for the first time by Kawanami et al. [3] at the Annual Meeting of the Canadian Association of Neuropathologists in September 1992. This …

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