Brain ubiquitin is markedly elevated in Alzheimer disease.

Levels of ubiquitin, microtubule associated protein tau and tubulin were determined by immunoassays in homogenates of cerebrum and cerebellum of Alzheimer disease and aged control cases. Ubiquitin levels increased many fold in the cerebral cortex of Alzheimer disease cases and the increase correlated strongly with the degree of neurofibrillary changes in the tissue. The increase in ubiquitin was much less remarkable in the cerebral white matter. Cerebellum which is unaffected with neurofibrillary changes in Alzheimer disease had normal levels of ubiquitin both in gray matter and in white matter. There was an appreciable increase in abnormally phosphorylated tau in an Alzheimer disease brain with severe neurofibrillary degeneration, whereas the normal tau levels were increased only slightly. Tubulin was slightly decreased in the cerebral gray matter but not in the adjacent white matter. Marked increase in brain ubiquitin in Alzheimer disease suggests the role of ubiquitin in the pathobiology of Alzheimer disease.