Involvement of NPY-immunoreactive neurons in the cerebral cortex of amyotrophic lateral sclerosis patients

We performed a quantitative histochemical study of neuropeptide Y (NPY) immunoreactivity in postmortem human brain to further define patterns of neuronal degeneration in amyotrophic lateral sclerosis (ALS). The density of NPY fibers was decreased in ALS motor cortex but not in other cortical regions or striatum. Although, the density of cortical NPY neurons was unchanged in high grade cases, neurons were shrunken and atrophic with pruned dendrites. NPY neurons are less severely affected than parvalbumin neurons which are severely depleted in ALS cortex. This differential involvement of local circuit neurons suggests that a simple excitotoxic model may not adequately explain patterns of neuronal loss in ALS.