Genetically identical twins show comparable tau PET load and spatial distribution.
Genetically identical twins show comparable tau PET load and spatial distribution.
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基因相同的双胞胎表现出相似的 tau PET 负载和空间分布。
DOI：
10.1093/brain/awac004
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发表时间：
2022-10-21
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影响因子：
--
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Tau的积累始于阿尔茨海默病的临床前阶段，与认知能力下降密切相关。为了预防的目的，重要的是要确定与tau累积和扩散相关的因素。研究遗传上的同卵双胞胎可能会深入了解遗传和环境对tau病理的贡献，因为同卵双胞胎的相似之处很大程度上是由遗传因素造成的，而同卵双胞胎的差异在很大程度上可以归因于非共有的环境因素。本研究旨在通过18F-flortaucipir正电子发射计算机断层扫描，检测一组遗传上相同的老年双胞胎在(I)tau负荷和(Ii)tau的空间分布方面的异同。我们选择了78对遗传完全相同的双胞胎(39对，平均年龄73±6岁)，他们都是淀粉样蛋白-β病理和载脂蛋白ε4携带者，他们接受了动态18F-flortaucipir PET检查。我们提取了内嗅觉、颞叶、广泛的新皮质和全球区域的结合电位(BPND)，并使用年龄和性别校正的类内相关性来检验BPND的对内相似性。此外，我们测试了与非双胞胎对相比，双胞胎对是否显示出更相似的18F-flortaucipir空间分布，以及是否可以仅基于18F-flortaucipir的空间分布来识别参与者的同卵双胞胎。最后，我们探索了环境因素(如体力活动、肥胖)是否可以解释18F-flortaucipir BPND中观察到的双胞胎差异。在肉眼检查中，观察到了类似阿尔茨海默病的18F-flortaucipir PET图谱，尽管我们主要确定了双胞胎中的相似之处，但一些对显示出强烈的不同之处。18F-flortaucipir BPND在内嗅区(r=0.40；P=0.01)、新皮质(r=0.59；P<；0.01)和全脑区(r=0.56；P<；0.01)呈正相关，而在颞区(r=0.20；P=0.10)无相关性。在校正了靶外结合的代理后，18F-flortaucipir在同一对双胞胎之间的分布模式[平均r=0.27；标准差(SD)=0.09]显著高于参与者的非双胞胎对之间(平均r=0.01；SD=0.10)(P<；0.01)。基于18F-flortaucipir的空间分布，我们可以识别属于同一对的双胞胎，准确率为86%。最后，18F-Folortaucipir BPND的对内差异与抑郁症状(0.37；β<；0.56)、体力活动(−0.41<；β<；−0.42)和社会活动(−0.32<；β<；−0.36)的对内差异有关(均P<；0.05)。总体而言，同卵双胞胎在tau负荷和空间分布上具有可比性，突出了遗传因素在tau病理积累和传播中的重要作用。考虑到同卵双胞胎中tau病理的不同，我们的结果还支持(潜在地可改变的)环境因素在阿尔茨海默病病理过程中的作用，这可能对未来的预防策略感兴趣。Coomans等人。揭示了同卵双胞胎在tau负荷和空间分布上的本质相似性，并表明他们可以根据tau的空间分布来识别双胞胎对。然而，配对内的差异--特别是tau负荷--也表明(可改变的)环境因素在tau积累中扮演了一个角色。
Tau accumulation starts during the preclinical phase of Alzheimer’s disease and is closely associated with cognitive decline. For preventive purposes, it is important to identify factors associated with tau accumulation and spread. Studying genetically identical twin-pairs may give insight into genetic and environmental contributions to tau pathology, as similarities in identical twin-pairs largely result from genetic factors, while differences in identical twin-pairs can largely be attributed to non-shared, environmental factors. This study aimed to examine similarities and dissimilarities in a cohort of genetically identical older twin-pairs in (i) tau load; and (ii) spatial distribution of tau, measured with 18F-flortaucipir PET. We selected 78 genetically identical twins (39 pairs; average age 73 ± 6 years), enriched for amyloid-β pathology and APOE ε4 carriership, who underwent dynamic 18F-flortaucipir PET. We extracted binding potentials (BPND) in entorhinal, temporal, widespread neocortical and global regions, and examined within-pair similarities in BPND using age and sex corrected intra-class correlations. Furthermore, we tested whether twin-pairs showed a more similar spatial 18F-flortaucipir distribution compared to non-twin pairs, and whether the participant’s co-twin could be identified solely based on the spatial 18F-flortaucipir distribution. Last, we explored whether environmental (e.g. physical activity, obesity) factors could explain observed differences in twins of a pair in 18F-flortaucipir BPND. On visual inspection, Alzheimer’s disease-like 18F-flortaucipir PET patterns were observed, and although we mainly identified similarities in twin-pairs, some pairs showed strong dissimilarities. 18F-flortaucipir BPND was correlated in twins in the entorhinal (r = 0.40; P = 0.01), neocortical (r = 0.59; P < 0.01) and global (r = 0.56; P < 0.01) regions, but not in the temporal region (r = 0.20; P = 0.10). The 18F-flortaucipir distribution pattern was significantly more similar between twins of the same pair [mean r = 0.27; standard deviation (SD) = 0.09] than between non-twin pairings of participants (mean r = 0.01; SD = 0.10) (P < 0.01), also after correcting for proxies of off-target binding. Based on the spatial 18F-flortaucipir distribution, we could identify with an accuracy of 86% which twins belonged to the same pair. Finally, within-pair differences in 18F-flortaucipir BPND were associated with within-pair differences in depressive symptoms (0.37 < β < 0.56), physical activity (−0.41 < β < −0.42) and social activity (−0.32 < β < −0.36) (all P < 0.05). Overall, identical twin-pairs were comparable in tau load and spatial distribution, highlighting the important role of genetic factors in the accumulation and spreading of tau pathology. Considering also the presence of dissimilarities in tau pathology in identical twin-pairs, our results additionally support a role for (potentially modifiable) environmental factors in the onset of Alzheimer’s disease pathological processes, which may be of interest for future prevention strategies. Coomans et al. reveal substantial similarities in tau load and spatial distribution in identical twins, and show that they can identify pairs of twins based on tau spatial distribution. However, within-pair differences—particularly in tau load—also suggest a role for (modifiable) environmental factors in tau accumulation.
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影响因子：
14.5
作者：
Franzmeier, Nicolai;Rubinski, Anna;Ewers, Michael
通讯作者：
Ewers, Michael
影响因子：
120.7
作者：
Jansen, Willemijn J.;Ossenkoppele, Rik;Knol, Dirk L.;Tijms, Betty M.;Scheltens, Philip;Verhey, Frans R. J.;Visser, Pieter Jelle
通讯作者：
Visser, Pieter Jelle
DOI：
10.2967/jnumed.118.211532
发表时间：
2019-04
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Collij LE;Konijnenberg E;Reimand J;Kate MT;Braber AD;Lopes Alves I;Zwan M;Yaqub M;van Assema DME;Wink AM;Lammertsma AA;Scheltens P;Visser PJ;Barkhof F;van Berckel BNM
通讯作者：
van Berckel BNM
DOI：
10.1186/s13195-018-0406-7
发表时间：
2018-08-04
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Konijnenberg E;Carter SF;Ten Kate M;den Braber A;Tomassen J;Amadi C;Wesselman L;Nguyen HT;van de Kreeke JA;Yaqub M;Demuru M;Mulder SD;Hillebrand A;Bouwman FH;Teunissen CE;Serné EH;Moll AC;Verbraak FD;Hinz R;Pendleton N;Lammertsma AA;van Berckel BNM;Barkhof F;Boomsma DI;Scheltens P;Herholz K;Visser PJ
通讯作者：
Visser PJ
影响因子：
16.6
作者：
Arnatkeviciute A;Fulcher BD;Oldham S;Tiego J;Paquola C;Gerring Z;Aquino K;Hawi Z;Johnson B;Ball G;Klein M;Deco G;Franke B;Bellgrove MA;Fornito A
通讯作者：
Fornito A