Biochemical Differentiation of Cholinesterases from Normal and Alzheimers Disease Cortex

Abstract

In Alzheimer’s disease, histochemically visualized cholinesterases with altered pH optimum for activity and inhibitable by indoleamines and the protease inhibitor bacitracin emerge in association with plaques and tangles. It has been suggested that these cholinesterases may participate in the pathologic process. However, it is not known whether the properties of cholinesterases observed in Alzheimer’s disease are due to requirements of histochemical procedures or actual biochemical properties of these enzymes. Using biochemical assays of acetylcholinesterase and butyrylcholinesterase activities, we demonstrate here that serotonin and bacitracin result in a significantly greater and dose-dependent inhibition of cholinesterases in Alzheimer’s disease cortex when compared with age-matched controls. In contrast, variations in pH did not distinguish cholinesterases in Alzheimer’s disease and control cortex. We also confirmed significant reduction of acetylcholinesterase activity in Alzheimer’s disease cortex and increased butyrylcholinesterase activity that only approached significance. We conclude that inhibition by indoleamines and bacitracin is a biochemical characteristic of a proportion of cholinesterases in Alzheimer’s disease that most likely represents the pool associated with plaques and tangles. Most of the available cholinesterase inhibitors are relatively incapable of inhibiting cholinesterases associated with plaques and tangles. The findings of the present investigation open the way for attempts to isolate cholinesterases associated with plaques and tangles and design or discovery of inhibitors specifically targeted to cholinesterases in these lesions.

Acetylcholinesterase Protein Level Is Preserved in the Alzheimer's Brain

“…In this context, AChE activity present in the AD brain associated with plaques and NFT display particular enzymatic properties and sensitivity to inhibitors (Geula and Mesulam, 1989;Wright et al, 1993). However, it is not clear whether the atypical histochemical behavior of AChE observed in AD is due to alterations in kinetic properties of these enzymes (Ciro et al, 2012), or due to interactions with other molecules within these lesions (Darvesh et al, 2010). In the context of the presence of AChE within plaques and NFT, it is important to note that both AD effectors, Aβ and abnormally hyperphosphorylated tau, can influence AChE levels in vitro (Sberna et al, 1997;Sáez-Valero et al, 2003;Hu et al, 2003;Melo et al, 2003) and in rodent models (Sberna et al, 1998;Sáez-Valero et al, 2002;Silveyra et al, 2012b;Kreutz et al, 2013).…”

Cholinesterase inhibitors isolated from bilberry fruit

“…As a result, memory loss is observed. Additionally, there is evidence that ChEs contribute to the formation of SP and NFT as well as to an increment of the toxicity of Aβ deposits (Ciro, Park, Burkhard, Yan, & Geula, 2012). Currently, cholinesterase inhibitors (ChEIs) are used for the elevation of ACh levels at cerebral cortex synapses.…”

Anti-diabetic and anti-Alzheimer’s disease activities of Angelica decursiva

“…Wherein more recent studies have shown that the AChE is localized mainly in the neurons, BChE is associated primarily with glial cells, endothelial cells, and neurons (Darvesh et al 2003). More importantly, AChE activity was shown to be reduced in the cortex, while BChE activity remained unchanged or increased during AD development (Ciro et al 2012).…”