M1 Agonists as a Potential Disease-Modifying Therapy for Alzheimers Disease

Antonella      Caccamo; Abraham      Fisher; Frank   M.   LaFerla

Abstract

Cholinergic deficit is a cardinal feature of Alzheimers disease, and cholinesterase inhibitors represent one of the most prominent means of mitigating this dysfunction. Cholinesterase inhibitors provide mild symptomatic relief, although they lose their efficacy over time most likely because they are not disease-modifying agents. An alternative strategy for restoring cholinergic function and attenuating the cognitive decline involves acting on the receptors on which acetylcholine acts. Stimulation of muscarinic acetylcholine receptors and in particular the M1 subtype has been shown to have a beneficial effect in restoring cognition in patients with Alzheimers disease and in attenuating Aβ and tau pathology in different animal models. In this review, we discuss the role of M1 agonists as a potential disease – modifying therapy for Alzheimers disease.

Keywords: M1 Agonists, Alzheimer's disease, cholinesterase inhibitors, acetylcholine receptors, cholinergic neurons