Evidence for an increased rate of choline efflux across erythrocyte membranes in Alzheimer's disease

Alzheimer's disease (AD), the major dementing disorder of the elderly, is associated with cholinergic neuronal loss and decreased activity of choline acetyl-transferase (CAT). Previous biophysical studies had suggested an altered conformation of membrane proteins in AD erythrocyte ghosts. Since erythrocytes have a choline transport system and cholinergic neurons are implicated in AD, the present experiments were undertaken to determine if the efflux rate of [¹⁴C]choline was altered in AD erythrocytes. The mean efflux rate constant was highly significantly increased (P<0.01) by greater than 25% in 9 drug-free AD patients compared to 9 sex-matched, drug-free controls of similar age. These results are discussed in terms of potential molecular mechanisms to account for cholinergic neuronal loss in AD.