Department of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada.
Division of Geriatric Medicine, Department of Medicine, Dalhousie University, Halifax, NS, Canada.
Neuropathol Appl Neurobiol. 2017 Dec;43(7):571-583. doi: 10.1111/nan.12423. Epub 2017 Jul 21.
Alzheimer's disease (AD) is characterized by cholinergic dysfunction and deposition of β-amyloid (Aβ) plaques and tau neurofibrillary tangles (NFTs) in the brain. Olfactory abnormalities often precede cognitive symptoms in AD, indicating early involvement of pathology in olfactory structures. The cholinergic system is important not only in cognition but also in modulation of the olfactory system. The primary olfactory gyrus (POG) is comprised of the olfactory tract, anterior olfactory nucleus (AON) and olfactory area (OA). Because of the importance of the olfactory and cholinergic systems, we examined the anatomical and cholinergic organization of the POG in normal human brain and neuropathology in AD.
Cytoarchitecture of the POG was studied using Nissl staining in normal (n = 8) and AD (n = 6) brains. Distributions of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were determined using histochemical methods. Aβ plaques and tau NFTs were detected using immunohistochemistry. Abundance of AD pathology was assessed using a semi-quantitative approach.
Nissl staining showed pyramidal cells in the AON and paleocortical organization of the OA. AChE stained neurons and neuropil in the AON and OA, while BChE activity was noted in the olfactory tract and in AON and OA neurons. Pathology was frequent in the AD POG and the abundance of BChE-associated AD pathology was greater than that associated with AChE.
AChE and BChE activities in normal POG recapitulated their distributions in other cortical regions. Greater abundance of BChE-associated, in comparison to AChE-associated, AD pathology in the POG suggests preferential involvement of BChE in olfactory dysfunction in AD.
阿尔茨海默病(AD)的特征是胆碱能功能障碍以及β-淀粉样蛋白(Aβ)斑块和 tau 神经原纤维缠结(NFTs)在大脑中的沉积。嗅觉异常通常先于 AD 的认知症状出现,表明病理学早期涉及嗅觉结构。胆碱能系统不仅在认知中很重要,而且在嗅觉系统的调节中也很重要。初级嗅觉回(POG)由嗅束、前嗅核(AON)和嗅觉区(OA)组成。由于嗅觉和胆碱能系统的重要性,我们检查了正常人类大脑和 AD 神经病理学中 POG 的解剖和胆碱能组织。
使用 Nissl 染色研究 POG 的细胞构筑,正常(n=8)和 AD(n=6)大脑。使用组织化学方法确定乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BChE)的分布。使用免疫组织化学检测 Aβ斑块和 tau NFT。使用半定量方法评估 AD 病理学的丰富度。
Nissl 染色显示 AON 中的锥体神经元和 OA 的古皮质组织。AChE 染色 AON 和 OA 中的神经元和神经原纤维,而 BChE 活性则在嗅束以及 AON 和 OA 神经元中被检测到。AD 病理学在 POG 中很常见,BChE 相关 AD 病理学的丰度大于 AChE 相关 AD 病理学的丰度。
正常 POG 中的 AChE 和 BChE 活性再现了它们在其他皮质区域的分布。与 AChE 相关的 AD 病理学相比,BChE 相关的 AD 病理学在 POG 中更为丰富,这表明 BChE 在 AD 嗅觉功能障碍中更优先参与。