Department of Psychiatry, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Neuropathology. 2011 Oct;31(5):503-9. doi: 10.1111/j.1440-1789.2010.01193.x. Epub 2011 Jan 27.
Alzheimer's disease (AD) is associated with neuronal degeneration, synaptic loss and deficits in multiple neurotransmitter systems. Alterations in the serotonin 1A (5-HT1A) receptor can contribute to impaired cognitive function in AD, and both in vitro binding and Positron emission tomography (PET) imaging studies have demonstrated that 5-HT1A receptors in the hippocampus/medial temporal cortex are affected early in AD. This neuropathological study examined the localization and immunoreaction intensity of 5-HT1A receptor protein in AD hippocampus with the goal to determine whether neuronal receptor levels are influenced by the severity of NFT severity defined by Braaks' pathological staging and to provide immunohistochemical confirmation of the binding assays and PET imaging studies. Subjects included AD patients and non-AD controls (NC) stratified into three Braaks' stages (Braak 0-II, NC; Braak III/IV and V/VI, AD). In the Braak 0-II group, 5-HT1A-immunoreactivity (ir) was prominent in the neuropil of the CA1 and subiculum, moderate in the dentate gyrus molecular layer (DGml), and low in the CA3 and CA4. No changes in 5-HT1A-ir were observed in the hippocampus of AD subjects in the Braak III/IV group. Hippocampal 5-HT1A-ir intensity was markedly decreased in the CA1 region in 6/11 (54.5%) subjects in the Braak V/VI group. Across all three groups combined, there was a statistically significant association between reduced 5HT1A-ir and neuronal loss in the CA1, but not in the CA3. The present data demonstrate that hippocampal 5-HT1A receptors are mainly preserved until the end-stage of NFT progression in AD. Thus, the utility of PET imaging using a 5-HT1A-specific radiolabeled probe as a marker of hippocampal neuronal loss may be limited to the CA1 field in advanced stage AD cases.
阿尔茨海默病（AD）与神经元变性、突触丧失和多种神经递质系统功能缺陷有关。5-羟色胺 1A（5-HT1A）受体的改变可能导致 AD 认知功能障碍，体外结合和正电子发射断层扫描（PET）成像研究表明，AD 早期海马/内侧颞叶皮质的 5-HT1A 受体受到影响。这项神经病理学研究检查了 AD 海马体中 5-HT1A 受体蛋白的定位和免疫反应强度，目的是确定神经元受体水平是否受到 NFT 严重程度的影响，NFT 严重程度由 Braaks 病理分期定义，并为结合测定和 PET 成像研究提供免疫组织化学证实。研究对象包括 AD 患者和非 AD 对照组（NC），分为三个 Braaks 分期（Braak 0-II，NC；Braak III/IV 和 V/VI，AD）。在 Braak 0-II 组中，5-HT1A 免疫反应性（ir）在 CA1 和下托的神经突中明显，在齿状回分子层（DGml）中中度，在 CA3 和 CA4 中较低。在 Braak III/IV 组的 AD 患者的海马体中未观察到 5-HT1A-ir 的变化。在 Braak V/VI 组的 11 名（54.5%）患者中，CA1 区的海马体 5-HT1A-ir 强度明显降低。在所有三组结合的情况下，减少的 5HT1A-ir 与 CA1 中的神经元丢失之间存在统计学显著关联，但在 CA3 中则没有。本数据表明，AD 中 NFT 进展的终末期，海马体 5-HT1A 受体主要得到保留。因此，使用 5-HT1A 特异性放射性示踪剂作为海马神经元丢失标志物的 PET 成像的实用性可能仅限于 AD 晚期病例的 CA1 区。
