Brain tissue from 12 subjects with pure Alzheimer's disease (AD) and 21 subjects with senile dementia of the Alzheimer type (SDAT) was investigated for membrane lipids and compared with that in age-matched controls. In brain tissue from the patients with AD, phospholipids were significantly decreased compared with that from SDAT patients and controls, cholesterol was reduced compared with that in controls, and gangliosides were significantly reduced in all gray-matter areas investigated compared with those in both SDAT subjects and controls. A reduction in gangliosides also occurred in the SDAT group, but it was smaller. In the white matter, the pattern of changes was the opposite. Phospholipids, cholesterol, cerebroside, and sulfatide were significantly reduced in the frontal-lobe white matter in the SDAT group compared with that in age-matched controls and AD patients. Gangliosides in the cerebrospinal fluid also separated AD from SDAT and controls. The findings indicate synapse degeneration as an important pathogenetic factor in AD. This disorder should be separated from SDAT, in which white-matter degeneration appears to be more prominent.