The cholinergic hypothesis is one of the earliest theories about the etiology of Alzheimer’s disease (AD). In the brain, acetylcholine (ACh) functions as both a neurotransmitter and neuromodulator. Cholinergic neurons are organized in nuclei and project across the entire central nervous system. They are involved in a number of cognitive processes including attention, learning, memory, and motivation. ACh mediates it effects through two receptor families, nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs). The cholinergic hypothesis links a deficit in cholinergic signaling to the cognitive decline seen in AD. Researchers identified a loss of cholinergic neurons throughout the basal forebrain of AD individuals, including in the nucleus basalis of Meynert, which is the main source of ACh in the brain. Research has also shown that cholinergic neurons are the first neurons affected by toxic Amyloid beta oligomers, and the cholinergic neurons that remain display decreased choline acetyltransferase (ChAT) activity. Additionally, there is a loss of neurons expressing nAChRs and mAChRs in AD brains. Several current AD treatments act by increasing cholinergic signaling. R&D Systems offers a range of research tools needed for investigating the role of the cholinergic system in AD.