Vogt B A, Crino P B, Vogt L J
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27103.
Cereb Cortex. 1992 Nov-Dec;2(6):526-35. doi: 10.1093/cercor/2.6.526.
Pathology related to dementia of the Alzheimer type (DAT) develops later in cingulate cortex than in medial temporal areas. Therefore, end-stage cases have earlier forms of pathology in cingulate cortex, and postmortem studies of this region may provide a window on processes that temporal cortices pass through decades before death. Five classes of DAT have been described on the basis of neuron degeneration and receptor binding in posterior cingulate cortex. The present study assessed binding of 3H-oxotremorine-M with pirenzepine (OXO-M/PZ), a protocol for presynaptic muscarinic receptors, and thioflavin S-stained neuritic plaques (NPs) in cingulate area 23a in 12 DAT cases distributed over four classes of pathology and in nine age-matched control cases. OXO-M/PZ binding was significantly elevated in layers I, II, IV, and VI of all DAT cases and was very high in layer V compared to control cases. Almost 75% of the layer Va increase was due to binding in classes 2 and 3, while classes 1 and 4 were least affected. In class 3 cases, neuron density in layer Va was inversely correlated with OXO-M/PZ binding (r = -0.98) and primitive NP densities (r = -0.93). The close association between neuron densities and presynaptic muscarinic ligand binding in some classes confirms that there are independent classes of DAT. The high and inverse correlations between cortical pathology and ligand binding in class 3 cases suggest that there is a progression in class 3 pathology. Finally, elevated OXO-M/PZ binding and a report of increased choline uptake suggest that cholinergic axons sprout in DAT, and this sprouting may be associated with a progressive loss of postsynaptic elements.
与阿尔茨海默型痴呆（DAT）相关的病理学变化在扣带回皮质中出现的时间比在内侧颞叶区域要晚。因此，终末期病例在扣带回皮质中存在早期形式的病理学变化，对该区域的尸检研究可能为颞叶皮质在死亡前数十年所经历的过程提供一个窗口。基于后扣带回皮质中的神经元变性和受体结合情况，已描述了五类DAT。本研究评估了12例分布在四类病理学情况中的DAT病例以及9例年龄匹配的对照病例的扣带区23a中3H-氧代震颤素-M与哌仑西平（OXO-M/PZ）（一种用于突触前毒蕈碱受体的检测方法）的结合情况以及硫黄素S染色的神经炎性斑块（NP）。与对照病例相比，所有DAT病例的I、II、IV和VI层中OXO-M/PZ结合显著升高，V层中非常高。V层a的增加近75%是由于2类和3类中的结合，而1类和4类受影响最小。在3类病例中，V层a的神经元密度与OXO-M/PZ结合（r = -0.98）和原始NP密度（r = -0.93）呈负相关。某些类别中神经元密度与突触前毒蕈碱配体结合之间的密切关联证实了存在独立的DAT类别。3类病例中皮质病理学与配体结合之间的高负相关性表明3类病理学存在进展。最后，OXO-M/PZ结合升高以及胆碱摄取增加的报告表明DAT中胆碱能轴突发芽，并且这种发芽可能与突触后元件的逐渐丧失有关。
