Molecular imaging of the association between serotonin degeneration and beta-amyloid deposition in mild cognitive impairment.
Molecular imaging of the association between serotonin degeneration and beta-amyloid deposition in mild cognitive impairment.
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DOI：
10.1016/j.nicl.2023.103322
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发表时间：
2023
影响因子：
4.2
通讯作者：
Chen, Kewei
中科院分区：
文献类型：
--
作者：
Smith, Gwenn S.;Protas, Hillary;Kuwabara, Hiroto;Savonenko, Alena;Nassery, Najlla;Gould, Neda F.;Kraut, Michael;Avramopoulos, Dimitri;Holt, Daniel;Dannals, Robert F.;Nandi, Ayon;Su, Yi;Reiman, Eric M.;Chen, Kewei
先前的研究显示转基因淀粉样蛋白小鼠模型中的5-羟色胺变性。5-HTT降低和淀粉样蛋白增加的模式将MCI与对照区分开来。5-HTT降低和淀粉样蛋白增加与MCI的记忆缺陷相关。在阿尔茨海默病（AD）和轻度认知障碍（MCI）中已经观察到5-羟色胺系统的退化。在转基因淀粉样蛋白小鼠模型中，在广泛的皮质β-淀粉样蛋白（Aβ）沉积之前检测到5-羟色胺变性，这也表明在临床前AD中可能观察到5-羟色胺变性。在一组MCI患者和一组健康老年人中，使用正电子发射断层扫描测量了5-羟色胺变性（反映为5-羟色胺转运体（5-HTT）的丢失）相对于Aβ沉积的分布差异。应用多模态偏最小二乘（mmPLS）算法来识别5-HTT可用性和Aβ沉积之间的空间协方差模式。研究了45名MCI患者和35名健康老年人，其中22人和27人分别被纳入“淀粉样蛋白阳性”和“淀粉样蛋白阴性”的分析。MCI组与健康老年对照组相比，皮质、皮质下和边缘系统5-HTT可用性较低，皮质Aβ沉积较高。在MCI组中，这种模式的更高表达与记忆和执行功能的更大缺陷相关，而在对照组中则不然。在MCI组中观察到的5-HTT可用性和Aβ沉积较低的空间协方差模式比对照组更大，并且与MCI组的认知功能障碍相关。结果支持mmPLS用于了解临床前AD过程中与Aβ沉积相关的神经化学变化。
Previous studies show serotonin degeneration in transgenic amyloid mouse models. A pattern of decreased 5-HTT and increased amyloid distinguishes MCIs from controls. Decreased 5-HTT and increased amyloid is correlated with memory deficits in MCI. Degeneration of the serotonin system has been observed in Alzheimer’s disease (AD) and in mild cognitive impairment (MCI). In transgenic amyloid mouse models, serotonin degeneration is detected prior to widespread cortical beta-amyloid (Aβ) deposition, also suggesting that serotonin degeneration may be observed in preclinical AD. The differences in the distribution of serotonin degeneration (reflected by the loss of the serotonin transporter, 5-HTT) relative to Aβ deposition was measured with positron emission tomography in a group of individuals with MCI and a group of healthy older adults. A multi-modal partial least squares (mmPLS) algorithm was applied to identify the spatial covariance pattern between 5-HTT availability and Aβ deposition. Forty-five individuals with MCI and 35 healthy older adults were studied, 22 and 27 of whom were included in the analyses who were “amyloid positive” and “amyloid negative”, respectively. A pattern of lower cortical, subcortical and limbic 5-HTT availability and higher cortical Aβ deposition distinguished the MCI from the healthy older control participants. Greater expression of this pattern was correlated with greater deficits in memory and executive function in the MCI group, not in the control group. A spatial covariance pattern of lower 5-HTT availability and Aβ deposition was observed to a greater extent in an MCI group relative to a control group and was associated with cognitive impairment in the MCI group. The results support the application of mmPLS to understand the neurochemical changes associated with Aβ deposition in the course of preclinical AD.
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影响因子：
5.3
作者：
Cho, Seongeun;Hu, Yun
通讯作者：
Hu, Yun
影响因子：
4.7
作者：
BOWEN, DM;ALLEN, SJ;DAVISON, AN
通讯作者：
DAVISON, AN
影响因子：
3.6
作者：
Benedict, RHB;Schretlen, D;Shpritz, B
通讯作者：
Shpritz, B
影响因子：
9.9
作者：
Cirrito JR;Wallace CE;Yan P;Davis TA;Gardiner WD;Doherty BM;King D;Yuede CM;Lee JM;Sheline YI
通讯作者：
Sheline YI
影响因子：
4.8
作者：
FOLSTEIN, MF;FOLSTEIN, SE;MCHUGH, PR
通讯作者：
MCHUGH, PR