Functional Changes in Muscarinic Receptors on Lymphocytes in Normal Aging and Alzheimer's Disease

Abstract

To demonstrate that muscarinic acetylcholine receptor (mAChR) acts as an aging marker, we studied whether receptor binding capacities decreased with age. A potent muscarinic cholinergic ligand, N-methyl scopolamine (NMS), was used to detect how the binding capacities (Kd, Bmax) of the receptor changed with age. Using techniques developed for the study of mAChR in brain homogenate, direct binding to whole live lymphocytes was shown for the [3H\-NMS. Both groups of healthy female adults (40~49 years old, N=27) and probable Alzheimer's patients (54~71 years old, N=17) were examined. For the healthy controls, the regression equations are: Y=12.2X – 272.6 (Kd; r=0.453, p<0.05) Y=401X – 16, 302 (Bmax; r=0.387, p<0.05) in which, X and Y respectively represent the age of individuals and Kd (or Bmax). Hence, for patients with Alzheimer's disease, the correlations between Kd and age, and between Bmax and age, were weak (r=0.021, 0.032, not significant, respectively). Three age groups from healthy female adults were examined: 40~49 (N=9), 50–59 (N=8) and 60–69 years old (N=10). There were significant differences (p<0.05) between age groups 40~49 and 60~69 years old in both Kd and Bmax. Furthermore, significant change (p<0.05) with Bmax was obtained in lymphocytes from patients, compared to age-matched controls. These results suggest that muscarinic cholinergic binding by lymphocytes may serve as a useful peripheral marker, reflecting alterations associated with aging. © 1989, The Japan Geriatrics Society. All rights reserved.