Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
J Alzheimers Dis. 2011;26(3):457-66. doi: 10.3233/JAD-2011-110056.
The 5-HT4 receptor may play a role in memory and learning and 5-HT4 receptor activation has been suggested to modulate acetylcholine release and to reduce amyloid-β (Aβ) accumulation. The aim of this study was for the first time to investigate the in vivo cerebral 5-HT4 receptor binding in early Alzheimer disease (AD) patients in relation to cortical Aβ burden. Eleven newly diagnosed untreated AD patients (mean MMSE 24, range 19-27) and twelve age- and gender-matched healthy controls underwent a two-hour dynamic [11C]SB207145 PET scan to measure the binding potential of the 5-HT4 receptor. All AD patients and eight healthy controls additionally underwent a [11C]PIB PET scan to measure the cortical Aβ burden. When AD patients were defined on clinical criteria, no difference in cerebral 5-HT4 receptor binding between AD patients and healthy controls was found (p = 0.54). However, when individuals were reassigned to groups according to their amyloid status, the PIB-positive individuals had 13% higher 5-HT4 receptor levels than PIB-negative individuals (p = 0.02) and the importance of classification of groups is emphasized. The 5-HT4 receptor binding was a positively correlated to Aβ burden (p = 0.03) and negatively to MMSE score of the AD patients (p = 0.02). Our data suggests that cerebral 5-HT4 receptor upregulation starts at a preclinical stage of and continues while dementia is still at a mild stage, which contrasts other receptor subtypes. We speculate that this may either be a compensatory effect of decreased levels of interstitial 5-HT, an attempt to improve cognitive function, increase acetylcholine release or to counteract Aβ accumulation.
5-HT4 受体可能在记忆和学习中发挥作用，5-HT4 受体的激活被认为可以调节乙酰胆碱的释放，并减少淀粉样蛋白-β（Aβ）的积累。本研究的目的是首次调查早期阿尔茨海默病（AD）患者体内的 5-HT4 受体与皮质 Aβ负担的关系。11 名新诊断的未经治疗的 AD 患者（平均 MMSE 为 24，范围为 19-27）和 12 名年龄和性别匹配的健康对照者进行了两小时的[11C]SB207145 PET 扫描，以测量 5-HT4 受体的结合潜能。所有 AD 患者和 8 名健康对照者还进行了[11C]PIB PET 扫描，以测量皮质 Aβ负担。当根据临床标准将 AD 患者定义为 AD 患者时，AD 患者与健康对照组之间的大脑 5-HT4 受体结合无差异（p=0.54）。然而，当根据淀粉样蛋白状态将个体重新分配到组中时，PIB 阳性个体的 5-HT4 受体水平比 PIB 阴性个体高 13%（p=0.02），并且强调了分组的重要性。5-HT4 受体结合与 Aβ 负担呈正相关（p=0.03），与 AD 患者的 MMSE 评分呈负相关（p=0.02）。我们的数据表明，大脑 5-HT4 受体的上调始于痴呆仍处于轻度阶段的临床前阶段，并持续存在，这与其他受体亚型形成对比。我们推测，这可能是由于间质 5-HT 水平降低的代偿性作用，试图改善认知功能，增加乙酰胆碱释放或对抗 Aβ 积累。
