[Changes of muscarinic cholinergic binding by human lymphocytes with normal aging and Alzheimer's disease]

A potent, new muscarinic cholinergic antagonist, L-[N-methyl-3H] quinuclidinyl benzilate methyl chloride ([3H-]-NM-QNB) was used to detect functional changes of muscarinic acetylcholine receptors (mAChR) on human lymphocytes in relation to age. Using techniques developed for the study of mAChR in brain homogenate, direct binding to whole live lymphocytes was shown for [3H]-NM-QNB. We examined Group of healthy adult females (41-66 years old, N = 34) and patients with "probable" Alzheimer's disease (55-75 years old, N = 11). It was shown that mAChR on lymphocytes were divided into two subtypes; high affinity (Ms) and low affinity types (Mw) for a ligand, [3H]-NM-QNB. For the healthy controls (age range 41-66 years old, N = 31), a negative correlation (r = -0.172) was found between Kd (Ms) and age. Also the negative correlation between Bmax (Ms) and age was shown to be weak (r = -0.164). The regression equations are: Y = 11.9X + 1306.4 (Kd(Ms); N = 31) Y = -80.6X + 8296.1 (Bmax(Ms); N = 31) where, X and Y designate the age of individuals and Kd (or Bmax), respectively. Hence, for patients with Alzheimer's disease, no significant changes with age in Kd (Ms) or Bmax (Ms) were obtained. Furthermore, correlations between the stage of clinical dementia of patients and Kd (Ms), and between the staging and Bmax (Ms) were shown to be strong (p less than 0.05). Significant change (p less than 0.05) in Bmax (Ms) was recognized in lymphocytes from patients with Alzheimer's disease (N = 11), compared with age-matched controls (N = 20).(ABSTRACT TRUNCATED AT 250 WORDS)