INTRODUCTIONWe investigated hippocampal synaptic density using synaptic vesicle 2A positron emission tomography (PET), and its association with amyloid beta (Aβ) and cognitive performance in healthy apolipoprotein E (APOE) ε4 carriers.METHODSSynaptic density was assessed in 46 individuals (APOE ε4/ε4 n = 14; APOE ε3/ε4 n = 16; APOE ε3/ε3 n = 16) with [11C]UCB‐J‐PET standardized uptake value ratios (SUVRs), by using the centrum semiovale as a reference region. Differences in hippocampal [11C]UCB‐J SUVRs were analyzed with analysis of variance (ANOVA) and linear models. Associations among [11C]UCB‐J SUVR, Aβ, hippocampal volume, and cognitive variables were analyzed with Spearman correlation.RESULTSHippocampal synaptic density was different among the APOE groups (PANOVA = 0.016): APOE ε4/ε4 carriers had lower [11C]UCB‐J SUVRs compared to APOE ε3/ε3 (p = 0.013). Hippocampal synaptic density did not correlate with Consortium to Establish a Registry for Alzheimer's Disease (CERAD) total score (rho = −0.052, p = 0.74), Alzheimer's Prevention Initiative Preclinical Cognitive Composite (APCC) score (rho = 0.17, p = 0.28), or [11C]PiB uptake (rho = −0.10, p = 0.50).DISCUSSIONHippocampal synaptic loss emerges early in the AD continuum and is measurable in vivo in cognitively unimpaired high‐risk individuals.Highlights Synaptic density was studied in vivo in healthy older adults using [11C]UCB‐J positron emission tomography. Apolipoprotein E (APOE) ε4/ε4 carriers had lower hippocampal synaptic density compared to APOE ε3/ε3. Synaptic density was not associated with cognitive performance in this population. Hippocampal synaptic alterations occur before clinical symptoms in APOE ε4/ε4 carriers.

中文翻译：

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SV2A PET 显示认知未受损的 APOE ε4/ε4 纯合子的海马突触丢失


引言我们使用突触小泡 2A 正电子发射断层扫描 （PET） 研究了海马突触密度，以及它与淀粉样蛋白 β （Aβ） 和健康载脂蛋白 E （APOE） ε4 携带者的认知能力的关联。方法在 46 例个体中评估了对称密度 （APOE ε4/ε4 n = 14;APOE ε3/ε4 n = 16;APOE ε3/ε3 n = 16），具有 [11C]UCB-J-PET 标准化摄取值比 （SUVR），使用半卵圆中心作为参考区域。使用方差分析 （ANOVA） 和线性模型分析海马 [11C]UCB-J SUVR 的差异。使用 Spearman 相关性分析 [11C]UCB-J SUVR 、 Aβ 、海马体积和认知变量之间的关联。结果APOE 组之间的半基突触密度不同 （PANOVA = 0.016）：与 APOE ε3/ε3 相比，APOE ε4/ε4 携带者的 [11C]UCB-J SUVR 较低 （p = 0.013）。海马突触密度与建立阿尔茨海默病登记处联盟 （CERAD） 总分 （rho = -0.052，p = 0.74）、阿尔茨海默病预防倡议临床前认知综合 （APCC） 评分 （rho = 0.17，p = 0.28） 或 [11C] PiB 摄取 （rho = -0.10，p = 0.50） 无关。讨论八肢突触丢失出现在 AD 连续体的早期，并且可以在认知未受损的高危个体体内测量。亮点 使用 [11C]UCB-J 正电子发射断层扫描在健康老年人体内研究了突触密度。与 APOE ε3/ε3 相比，载脂蛋白 E （APOE） ε4/ε4 载体的海马突触密度较低。突触密度与该人群的认知表现无关。海马突触改变发生在 APOE ε4/ε4 携带者临床症状之前。