Familial occurrence of amyotrophic lateral sclerosis, parkinsonism, and dementia.

We report here on a 59-year-old man from southwest Germany who died after a 14-year course of an illness characterized by progressive dementia, parkinsonism, and amyotrophic lateral sclerosis. Postmortem examination revealed Alzheimer's neurofibrillary tangles in the substantia nigra, innominata, locus ceruleus, parahippocampal gyrus, and less frequently in the hippocampus and the cerebral cortex. Investigation of the patient's pedigree back to the 17th century revealed nine additional family members who had exhibited signs of amyotrophic lateral sclerosis or parkinsonism-dementia or both. The pedigree suggests that a recessive trait with genetic epistasis is responsible for the disorder.