ALZHEIMERS-DISEASE - RELATIONSHIP BETWEEN MUSCARINIC CHOLINERGIC RECEPTORS, BETA-AMYLOID AND TAU-PROTEINS

Senile dementia is one of the most important health problems in develo ped countries. The main disease causing dementia is Alzheimer's diseas e that is characterized by the progressive deterioration of the cholin ergic system, beta-amyloid production and deposition, and neurofibrill ary tangle formation. Most of the reviewed data, along with data from experiments performed in our laboratory, suggest that there are no cha nges in the number of muscarinic receptors between Alzheimer and contr ol brains, although the receptors expressed in Alzheimer's disease bra ins can be anomalous in their function. The muscarinic receptor-G-prot ein interaction also seems to be impaired in Alzheimer's disease compa red with control brains, as well as the G-protein system, with an impo rtant decrease in the function of the Gq/11, the most important G-prot ein stimulating phosphoinositide hydrolysis in human brain; in additio n, the second messenger system is also impaired, with a decrease in th e synthesis of phosphoinositides and in the number of IP3 receptors. M uscarinic cholinergic receptors are also linked to beta-amyloid produc tion, stimulation of the M-1 subtype with agonists results in the proc essing of the beta-amyloid precursor protein to non-amyloidogenic prod ucts and administration of a fraction of the beta-amyloid (beta-amyloi d 25-35) to rats, results in a decrease in the number of muscarinic re ceptors in brain. M-1 agonists also decrease the phosphorylation of ta u proteins, playing again a modulatory role in the pathogenesis of Alz heimer's disease. The existence of a link between beta-amyloid and tau proteins also has been reported; treatment of hippocampal neurones wi th beta-amyloid, or the 25-35 residue fragment, resulted in an increas e in tau protein phosphorylation. The particular contribution of musca rinic receptors, beta-amyloid and tau proteins in the pathogenesis of Alzheimer's disease remains still unclear. Probably Alzheimer's diseas e could be due to a progressive degeneration in the relationship betwe en the three components covered in this review. (C) Elsevier, Paris.