Depression in Alzheimer’s Disease: The Roles of Cholinergic and Serotonergic Systems

Abstract

Although depression and Alzheimer' s disease fundamentally result from distinct pathophysiological events, their coincidence is far from a rare occurrence. In addition to the difficulty in the diagnosis of depression in the patients with a cognitive impairment, care givers and even physicians are mostly unaware that depression and Alzheimer' s disease can coexist. While depression has already a devastating impact on quality of life by itself, coinciding depression and Alzheimer' s disease may advance to a cataclysmic magnitude. This chapter underlines obstacles in the recognition of depression in the Alzheimer' s patients following a brief introduction to the concept of depression. Depression and Alzheimer' s disease appear to intersect in the cholinergic and serotonergic systems which may engender an exquisite strategy in the treatment of both disorders. Therefore, potential cholinergic and serotonergic targets are also emphasized.

Association Between the Cholinesterase Inhibitor Donepezil and the Cholinergic Precursor Choline Alphoscerate in the Treatment of Depression in Patients with Alzheimer’s Disease

“…It is also well known that the hippocampus is involved in depression as well as in cognitive dysfunctions. In AD it can represent a crossroad between behavioral and cognitive symptoms [ 66 ]. Furthermore, SSRI indirectly may act on the cholinergic system by increasing brain ACh levels by inhibiting the cholinesterase [ 67 ].…”

Methionine Capped Nanoparticles as Acetylcholinesterase Inhibitors

“…In these measurements, the enzyme concentration was constant and set to give an optimal spectrophotometric signal. Physiological effects were quantified as AChE inhibition, given as: AChE inhibition ¼ 100 � ðA 0 À AÞ=A 0 (1) where A 0 and A stand for the AChE activity in the absence of Lmethionine and Ag or Au @LM NPs. The activity was measured after the exposure to methionine, and Ag or Au @LM NPs, respectively.…”

“…Both conditions are strongly related to the level of the neurotransmitter acetylcholine. [1] The level of acetylcholine is regulated via acetylcholinesterase activity. Acetylcholinesterase (AChE) is an enzyme involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems.…”

“…Alzheimer's disease and depression are health conditions affecting millions of people worldwide. Both conditions are strongly related to the level of the neurotransmitter acetylcholine [1] . The level of acetylcholine is regulated via acetylcholinesterase activity.…”

From Hybrids to New Scaffolds: The Latest Medicinal Chemistry Goals in Multi-target Directed Ligands for Alzheimer’s Disease

“…On the other hand, many lifestyle modifications such as physical activity, sleep, feeding, smoking, alcohol, and intellectual stimulation are thought to have an impact cognitive impairment [ 12 ] even though more evidence is still needed. So far, AD has been related to several altered brain functions, including extracellular plaques containing abnormal deposits of beta-amyloid peptides [ 13 - 16 ], the hyperphosphorylated form of the microtubular Tau protein involving twisted fibers [ 17 - 20 ], inflammation [ 21 - 24 ], oxidative stress [ 25 - 28 ], cholinergic neuron damage (cholinergic hypothesis) [ 29 - 31 ], serotonin misregulation (serotoninergic hypothesis) [ 32 - 34 ], and many others [ 35 - 39 ].…”