2010 issue 2

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Volume 19, issue 2

Review article

Interactions between the cholinergic system and amyloid in the pathogenesis and treatment of Alzheimer’s disease: do cholinesterase inhibitors affect the natural course of the disease?

Tomasz Sobów1
1. Klinika Psychiatrii Wieku Podeszłego i Zaburzeń Psychotycznych, Centralny Szpital Kliniczny, Uniwersytet Medyczny w Łodzi
Postępy Psychiatrii i Neurologii 2010; 19(2): 157–164
Keywords: Alzheimer’s disease, amyloid, cholinergic system, cholinesterase inhibitors, natural course of disease

Abstract

Objectives. To present available research evidence suggesting a possibility of cholinergic modulation of β-APP metabolism and its theoretical implications for Alzheimer's disease treatment.
Views. Leading hypotheses concerning Alzheimer's disease (AD) consider dysfunction of β-APP metabolism as the basic pathogenic mechanism (the amyloid cascade hypothesis), and a cholinergic neurotransmission disorder as a neurochemical background for clinically observed cognitive and behavioral pathology (the cholinergic hypothesis). Molecular and clinical studies support the idea that β-APP metabolism products interact with the cholinergic system in a quite complicated manner. Beta-amyloid may be particularly toxic to cholinergic neurons, and may lead to a deficiency of acetylcholine biosynthesis. On the other hand, cholinergic dysfunction may lead to an overproduction and cerebral deposition of amyloid β.
Conclusions. Cholinesterase inhibitors facilitating neurotransmission within the cholinergic synapse may produce a more than symptomatic effect, possibly via modulation of β-APP metabolism. Although data obtained in recent years support the view about a possible effect of cholinesterase inhibitors on the natural course of AD, they are not conclusive yet.

Address for correspondence:
dr hab. n. med. Tomasz Sobów
Klinika Psychiatrii Wieku Podeszłego i Zaburzeń Psychotycznych UM
ul. Czechosłowacka 8/10, 92-216 Łódź
tel. 0-42-6757372
fax: 0-42-6757729
e-mail: tmsobow@csk.umed.lodz.pl