ALZHEIMER PATHOLOGY AND CHOLINESTERASES IN THE PRIMARY OLFACTORY GYRUS

Abstract

Olfactory dysfunction frequently occurs in Alzheimer's disease (AD), often manifesting before cognitive symptoms. Early deposition of AD pathology is observed in regions of the primary olfactory system, including the anterior olfactory nucleus (AON). AD pathology has been described in the bulbar (olfactory bulb) and peduncular (olfactory tract) AON. However, limited studies have examined the cortical portion within the primary olfactory gyrus (POG). Furthermore, despite the importance of the cholinergic system in AD, cholinesterases have not been explored in this region. This study looks to expand upon the anatomical and cholinergic organization of the POG in the normal brain and to describe the neuropathological changes that occur in this region in AD. Fourteen (8 normal and 6 AD) brain tissue cases were obtained from the Maritime Brain Tissue Bank. The anatomical organization of POG relative to surrounding tissues was studied using Nissl staining. POG tissues were examined for the distribution of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity using histochemical techniques. β-amyloid (Aβ) plaques and tau neurofibrillary tangles (NFTs) were detected using immunohistochemistry. The abundance of AD pathology was measured using a semi-quantitative approach. The POG is comprised of cortical AON and olfactory tract, ventrally, and paleocortical olfactory area (OA), dorsally. Abundant AChE activity, associated with neurons and neuropil, was detected in the AON and OA, with very little activity noted in the olfactory tract. In contrast, BChE activity was associated with neurons and microglia in the AON and OA, while activity was prominent in the olfactory tract. The AON and OA, showed frequent deposition of cholinesterase-associated AD pathology, for both Aβ plaques and tau NFTs. Distribution of AD pathology revealed a specific laminar pattern within the OA. The abundance of BChE-associated AD pathology was greater than that associated with AChE in the POG. AChE and BChE activities in the normal POG recapitulated similar distributions in other cortical and subcortical brain regions. In AD, there was greater abundance of BChE-associated plaques in comparison to AChE-associated plaques in the POG. This suggests that BChE-associated pathology contributes to olfactory dysfunction in AD. Further studies are required to elucidate its significance.