Klin Farmakol Farm. 2006;20(1):38-40

Is there a connection between statins and cholinergic system?

MUDr. Ľubica Cibičková¹, prof. MUDr. Vladimír Palička CSc²

¹ II. interní klinika LF UK a Fakultní nemocnice, Hradec Králové

² Ústav klinické biochemie a diagnostiky FN a LF UK Hradec Králové

Alzheimer´s disease (AD) is a progressive neurodegenerative disease characterized by degeneration and destruction of cholinergic nerve cells. Modern therapy of AD concentrates on influencing the cholinergic system by the inhibition of acetylcholinesterase (AChE). In a recent studies, hypolipidamics such as statins have been shown to have potency to attenuate the risk of AD. However, the exact mechanism of their action on AD has not been clarified yet. Firstly, they may influence of the brain cholinergic system by reducing apolipoprotein E (ApoE) synthesis, since statins inhibit the synthesis of ApoE in brain glia and an inverse correlation between ApoEε4 and cholinacetyltransferase (ChAT) activity was found. Administration of statins may augment ChAT activity by the inhibition of ApoE synthesis thereby increasing the amount of desirable acetylcholine (ACh) in synapses. Secondly, statins also lower the synthesis of cholesterol, a substance higher levels of which support the formation of amyloid beta (Aβ). Because Aβ reduces the degradation of acetylcholinesterase (AChE), statins might prevent this unfavourable build-up of AChE by suppressing the formation of Aβ. Moreover, levels of Aβ correlate with ChAT activity, that is why statins might, in addition, enhance desirable activity of ChAT, and hence, by this dual mechanism, contribute to the elevation of the amount of ACh available in synapses. In one paper, direct influence of some statins on cholinesterases has already been described.

In spite of the above-mentioned hypotheses about the potential influence of statins on cholinergic system in patients with AD, it cannot be excluded that statins affect AD in other ways such by their antiinflammatory effect and by up-regulation of nitric oxide synthesis. Futher studies are needed to elucidate the function of statins in the prevention and/or treatment of AD. In concert with that, the number of published papers on this theme shows an enormous interest of researchers in this drug group.

Keywords: Alzheimer´s disease, statins, cholinergic system

Published: March 1, 2006  Show citation