Nuclei extracted from neocortex of patients with Alzheimer's disease and treated with micrococcal nuclease release a population of dinucleosomes that contain an increase in the linker histones H1o and H1oo . Five other degenerative brain diseases that clinically resemble Alzheimer's disease do not result in these changes, although Pick's disease is associated with an increase in H1 on dinucleosomes. Histones from nuclei of patients with Alzheimer's disease are also more resistant to salt-induced release from chromatin than are those from age-matched control subjects. These results support the hypothesis that an alteration in chromatin structure is a marker for Alzheimer's disease.