Figure 1.

Several interacting factors can lead to the death of central cholinergic neurons. Aging with an increased microglial activation disrupted the blood-brain barrier and decreased neuronal plasticity provides a breeding ground to which environmental factors, such as stress or systemic inflammation, and genetic factors, such as loss of inhibition of neuroinflammatory process or abnormal protein leading to aggregates, are added. Cholinergic neurons are highly demanding in energy and highly sensitive to oxidative stress. The two main cholinergic populations of the central nervous system (CNS) are located to the brainstem (BS) and the basal forebrain (BF). The cholinergic neurons of the BF are projecting to the hippocampus (Hipp.) and throughout the neocortex. The cholinergic neurons of the BS are projecting to the thalamus (Thal.), the ventral tegmental area (VTA), and the BF. Death of BF cholinergic cells leads to a loss of acetylcholine (Ach) influx in the hippocampus which is involved in memory impairment but also relieves a brake on neuroinflammation. The loss of cholinergic input to the PFC leads to impaired executive function. Concerning cholinergic death in the BS, it raises the question of its association with the inaugural visual complaints expressed by Alzheimer patients as it controls ocular saccades. Finally, the death of central cholinergic neurons is associated with a temporoparietal hypometabolism.