On the Physiological Relevance of Muscarinic Acetylcholine Receptors in Alzheimer's Disease

The loss of cholinergic neurons, particularly in the forebrain, plays an important role in the pathophysiology of Alzheimer's disease (DAT). This concept has lead to the effective treatment of DAT by means of acetylcholine (Ach) esterase inhibitors. G-protein-coupled muscarinic acetylcholine receptors (mAchR) are classified in 5 subtypes, the M1 receptor stimulation and M2 inhibition being especially associated with cognitive skills. Modified cerebral muscarinic receptor profiles in patients with Alzheimer's disease in addition to loss of Ach releasing neurons help us to understand the pathophysiology of dementia and offer potential therapeutic approaches. Specific agonists and antagonists of muscarinic receptors are discussed as possible treatment options in DAT. Experimental results postulate a positive long lasting modulation of the pathological neuronal protein pattern in addition to their cholinomimetic effect.