Cholinergic dysfunction in diseases with Lewy bodies
Cholinergic dysfunction in diseases with Lewy bodies
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DOI：
10.1212/wnl.54.2.407
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发表时间：
2000-01-25
期刊：
影响因子：
9.9
通讯作者：
Corey-Bloom, J
中科院分区：
文献类型：
--
作者：
Tiraboschi, P;Hansen, LA;Corey-Bloom, J
目的：评估路易体疾病（LB；AD 的 LB 变体 [LBV]、弥漫性 LB 病 [DLBD] 和帕金森病 [PD]）的胆碱能活性，以确定 1) AD 变化是否是胆碱能功能障碍所必需的，2) 新皮质和古皮质区域胆碱能活性下降相同程度，以及 3) 胆碱能丧失受 APOE 基因型影响，背景：像AD、LB 疾病与胆碱乙酰转移酶 (ChAT) 活性降低有关。据报道，LBV 中 APOE epsilon 4 等位基因频率增加。 APOE 基因型是否影响 LBV 的胆碱能功能尚不清楚。方法：对 182 名 AD（美国国家老龄化研究所建立阿尔茨海默病标准登记协会）、49 名 LBV、11 名 PD、6 名 DLBD 和 16 名正常对照 (NC) 受试者进行尸检。测定中额叶和海马皮质中的 APOE 基因型和 ChAT 活性 (nmol/h/100 mg)。结果：与 NC（255.4 +/- 134.6；p < 0.001）和 AD（122.6 +/- 78.9；p < 0.001）相比，LB 疾病（LBV：53.3 +/- 39.0；PD：54.8 +/- 35.7；DLBD：41.3 +/- 24.8）的平均中额叶 ChAT 活性显着降低。 0.05），在 LB 疾病中，患有（LBV）和不患有（DLBD 和 PD）AD 病理的患者的中额叶 ChAT 活性下降程度相似。尽管中额皮质中 LBV 的平均 ChAT 活性不到 AD 的一半，但其与海马中的 AD 相似（LBV：243.5 +/- 189,7；AD：322.8 +/- 265.6；p > 0.05）。然而，AD 和 LBV 的海马 ChAT 活性均低于 NC 的海马 ChAT 活性 (666.5 +/- 360.3；p < 0.001)。 epsilon 4 等位基因剂量不影响 LBV 中额叶 ChAT 活性。结论：LB 疾病中额叶中 ChAT 活性显着丧失，与共存的 AD 变化无关。与海马相比，中额叶更大的胆碱能缺陷可以将 LBV 与 AD 区分开来。 epsilon 4 等位基因剂量与中额叶 ChAT 活性之间缺乏关系表明其他因素可能在 LBV 下降中发挥作用。
Objective: To evaluate cholinergic activity in diseases with Lewy bodies (LB; LB variant of AD [LBV], diffuse LB disease [DLBD], and Parkinson's disease [PD]) to determine if 1) AD changes are requisite to cholinergic dysfunction, 2) cholinergic activity declines to the same extent in neocortical and archicortical areas, and 3) cholinergic loss is influenced by APOE genotype, Background: Like AD, diseases with LB are associated with decreased choline acetyltransferase (ChAT) activity. Increased APOE epsilon 4 allele frequency has been reported in LBV. Whether APOE genotype affects cholinergic function in LBV remains unclear. Methods: An autopsy series of 182 AD (National Institute on Aging and Consortium to Establish a Registry for Alzheimer's Disease criteria), 49 LBV, 11 PD, 6 DLBD, and 16 normal control (NC) subjects. APOE genotype and ChAT activity (nmol/h/100 mg) in the midfrontal and hippocampal cortices were determined. Results: Mean midfrontal ChAT activity was markedly reduced in diseases with LB (LBV: 53.3 +/- 39.0; PD: 54.8 +/- 35.7; DLBD: 41.3 +/- 24.8) compared to NC (255.4 +/- 134.6; p < 0.001) and AD (122.6 +/- 78.9; p < 0.05), Among diseases with LB, midfrontal ChAT activity was decreased to a similar extent in patients with (LBV) and without (DLBD and PD) AD pathology. Although mean ChAT activity for LBV was less than half that for AD in the midfrontal cortex, it was similar to that for AD in the hippocampus (LBV: 243.5 +/- 189,7; AD: 322.8 +/- 265.6; p > 0.05). However, hippocampal ChAT activity for both AD and LBV was lower than that for NC (666.5 +/- 360.3; p < 0.001). The epsilon 4 allele dosage did not influence midfrontal ChAT activity in LBV, Conclusions: Marked losses in midfrontal ChAT activity occur in diseases with LB, independent of coexistent AD changes. A greater midfrontal, as opposed to hippocampal, cholinergic deficit may differentiate LBV from AD. The lack of a relationship between epsilon 4 allele dosage and midfrontal ChAT activity suggests that other factors may play a role in its decline in LBV.