Cholinesterases in normal and Alzheimer's disease primary olfactory gyrus
The olfactory system begins at the olfactory epithelium in the nasal cavity, where olfactory sensory neurons project to the olfactory bulb. Neurons within the olfactory bulb project, via the olfactory tract, to the primary olfactory cortex, which includes the olfactory tubercle and piriform cortex (Figure 1) 5. In addition, a region of the primary olfactory system, a gyrus comprised of the olfactory tract, clusters of pyramidal neurons that form the cortical anterior olfactory nucleus (AON) and the olfactory area (OA) 5, has been described previously. Because this gyrus is the focus of the present work, as outlined below, for ease of reference, we will refer to this region as the primary olfactory gyrus (POG).
The AON is divided into three parts: bulbar (within the olfactory bulb), peduncular (within the olfactory tract) and cortical (within the POG) (Figure 1) 5. Early deposition of AD pathology has been reported in the bulbar and peduncular AON 2. Few studies have examined AD pathology in components of the POG 14, the entry point of olfactory sensory input into the cerebral cortex. Furthermore, despite the importance of the cholinergic system in AD 17, changes to components of the cholinergic system in the POG of individuals with AD have not been explored.
AD is characterized, not only by the presence of Aβ and NFT deposition, but also by the loss of cholinergic neurons, the neurotransmitter acetylcholine, its synthesizing enzyme, choline acetyltransferase and the degrading enzyme acetylcholinesterase (AChE) 18. In contrast, activity of the related enzyme, butyrylcholinesterase (BChE) in AD, has been observed to increase 18 or remain the same 23. In AD, Aβ plaques and NFTs have been shown to associate with cholinesterase activity, particularly with BChE 24. BChE appears to play a role in the conversion of benign plaques, as seen in normal ageing, to fibrillar plaques present in AD 27. Support for this role comes from the observation that the association of BChE with Aβ plaques is also found in mouse models of AD 28. Moreover, in an AD mouse model, wherein the BChE gene has been knocked out, a decrease in the deposition of Aβ plaques has been observed 29.
In this study, we first examined the cytoarchitecture and the distribution of AChE and BChE in the normal human POG. In addition, we examined Aβ plaque and NFT deposition in the POG of individuals with AD. As α‐synuclein‐positive Lewy bodies and Lewy neurites are frequently observed in the brains of moderate to severe cases of AD 31, we also stained for α‐synuclein‐associated pathologies in the AD POG. Because the cholinergic system is affected in AD, we examined the association of both AChE and BChE with Aβ plaques, tau NFTs and α‐synuclein pathologies.