[Anticholinesterases in the treatment of Alzheimer's disease]

Among the numerous pathophysiological theories that attempt to explain the development of Alzheimer's disease (AD) there are two facts that stand out above the rest: on the one hand, the formation of neurofibrillary tangles inside cells and, on the other, the extra-cellular deposition of beta-amyloid protein. These two mechanisms lead to neurodegeneration and the death of cells by means of a process called 'apoptosis' or 'programmed cell death'. In the early stages of this neurodegenerative process it is more pronounced in cholinergic-type brain centres. This led to the formulation of the so-called cholinergic theory of Alzheimer, which provides the rationale behind the use of the drugs that are currently available to treat this disease, namely, acetylcholine esterase (AChE) inhibitors (rivastigmine, donepezil and galanthamine).

We review the possible pharmacological approaches that could help to prevent or delay cell death, and which act on the mechanisms involved in the production of neurofibrillary tangles or the deposition of beta-amyloid protein. We also review the main characteristics of cholinergic neurotransmission, which will help us to understand the therapeutic approaches that have been applied in an attempt to enhance deficient cholinergic neurotransmission. One of the most notable of these is the amount of attention recently being paid to the enzyme AChE, which increases the bioavailability of the neurotransmitter in the cholinergic synapses by preventing the hydrolysis of acetylcholine; these are the only drugs currently available for the symptomatic treatment of this disease.