Decreased cerebral α4β2* nicotinic acetylcholine receptor availability in patients with mild cognitive impairment and Alzheimer's disease assessed with positron emission tomography
Decreased cerebral α4β2* nicotinic acetylcholine receptor availability in patients with mild cognitive impairment and Alzheimer's disease assessed with positron emission tomography
复制标题
DOI：
10.1007/s00259-010-1644-5
复制
发表时间：
2011-03-01
影响因子：
9.1
通讯作者：
Sabri, Osama
中科院分区：
文献类型：
--
作者：
Kendziorra, Kai;Wolf, Henrike;Sabri, Osama
尸检研究表明，阿尔茨海默病(AD)患者存在烟碱型乙酰胆碱受体(NAChRs)缺失。为了确定这些胆碱能系统的改变是否发生在AD的早期阶段，我们对轻中度AD患者和有高进展到AD风险的遗忘性轻度认知障碍(MCI)患者进行了α4β2*烟碱型乙酰胆碱受体(α4β2*nAChR)的正电子发射断层扫描(PET)。8例轻度脑梗塞患者和7例年龄匹配的健康对照组接受2-[(18)F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine(2-[(18)F]FA-85380)正电子发射计算机断层扫描。与个人磁共振成像配准后，计算2-[(18)F]FA-85380的结合电势(BP(ND))。通过感兴趣区分析和基于体素的分析，发现阿尔茨海默病和轻度认知障碍患者的典型AD脑区2-[(18)F]FA-85380 BP(ND)显著降低。由此可见，最合适的参照区是胼胝体。2-[(18)F]FA-85380 BP(ND)与认知功能障碍的严重程度相关。2-[(18)F]FA-85380碱基(ND).2-[(18)F]FA-85380正电子发射计算机断层扫描是检测阿尔茨海默病患者α4β2*nAChRs降低的一种敏感而可行的方法。此外，2-[(18)F]FA-85380正电子发射计算机断层扫描可提供从轻度脑梗塞转为AD的预后信息。
Postmortem studies indicate a loss of nicotinic acetylcholine receptor (nAChRs) in Alzheimer's disease (AD). In order to establish whether these changes in the cholinergic system occur at an early stage of AD, we carried out positron emission tomography (PET) with a specific radioligand for the alpha 4 beta 2* nicotinic acetylcholine receptor (alpha 4 beta 2* nAChR) in patients with mild to moderate AD and in patients with amnestic mild cognitive impairment (MCI), who have a high risk to progress to AD.Nine patients with moderate AD, eight patients with MCI and seven age-matched healthy controls underwent 2-[(18)F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[(18)F]FA-85380) PET. After coregistration with individual magnetic resonance imaging the binding potential (BP(ND)) of 2-[(18)F]FA-85380 was calculated using either the corpus callosum or the cerebellum as reference regions. PET data were analysed by region of interest analysis and by voxel-based analysis.Both patients with AD and MCI showed a significant reduction in 2-[(18)F]FA-85380 BP(ND) in typical AD-affected brain regions. Thereby, the corpus callosum was identified as the most suitable reference region. The 2-[(18)F]FA-85380 BP(ND) correlated with the severity of cognitive impairment. Only MCI patients that converted to AD in the later course (n = 5) had a reduction in 2-[(18)F]FA-85380 BP(ND).2-[(18)F]FA-85380 PET appears to be a sensitive and feasible tool for the detection of a reduction in alpha 4 beta 2* nAChRs which seems to be an early event in AD. In addition, 2-[(18)F]FA-85380 PET might give prognostic information about a conversion from MCI to AD.