Increased in vitro phosphorylation of a Mr 60,000 protein in brain from patients with Alzheimer disease.

We have established in vitro conditions under which we can reliably measure kinase activity in normal postmortem human brain. Using these conditions, we detected in the brains of patients with Alzheimer disease a 2-fold increase in the level of Mr 60,000 protein phosphorylation compared to age-matched controls. The Mr 60,000 protein phosphorylation was found exclusively in the cytosol fraction. No differences were detected between phosphoproteins in 100,000 X g pellet fractions from brains of Alzheimer disease patients and from age-matched controls. Postmortem time up to 17 hr does not seem to affect the phosphorylation level of the Mr 60,000 protein. Younger Alzheimer disease patients had more prominent changes in the elevation of the Mr 60,000 protein phosphorylation level than older patients, although in the control patient, age did not affect the phosphorylation level of the Mr 60,000 protein. We conclude that in the brain cytosol of Alzheimer disease there may be an abnormality in either the degree of Mr 60,000 protein phosphorylation or in the Mr 60,000 protein concentration.