Schaeverbeke Jolien, Luckett Emma S, Gabel Silvy, Reinartz Mariska, De Meyer Steffi, Cleynen Isabelle, Sleegers Kristel, Van Broeckhoven Christine, Bormans Guy, Serdons Kim, Van Laere Koen, Dupont Patrick, Vandenberghe Rik
Department of Neurosciences, Laboratory for Cognitive Neurology Leuven Brain Institute, KU Leuven Leuven Belgium.
Department of Imaging and Pathology, Laboratory of Neuropathology Leuven Brain Institute, KU Leuven Leuven Belgium.
Alzheimers Dement (N Y). 2022 Feb 23;8(1):e12227. doi: 10.1002/trc2.12227. eCollection 2022.
The bridging integrator 1( rs744373 risk polymorphism has been linked to increased [F]AV1451 signal in non-demented older adults (ie., mild cognitive impairment [MCI] plus cognitively normal [CN] individuals). However, the association of with in vivo tau, amyloid beta (Aβ) burden, and cognitive impairment in the asymptomatic stage of Alzheimer's disease (AD) remains unknown.
The effect on [F]AV1451 binding was evaluated in 59 cognitively normal (CN) participants (39% apolipoprotein E [ ε4]) from the Flemish Prevent AD Cohort KU Leuven (F-PACK), as well as in 66 Alzheimer's Disease Neuroimaging Initiative (ADNI) CN participants, using voxelwise and regional statistics. For comparison, 52 MCI patients from ADNI were also studied.
Forty-four percent of F-PACK participants were rs744373 risk-allele carriers, 21% showed high amyloid burden, and 8% had elevated [F]AV1451 binding. In ADNI, 53% and 50% of CNs and MCIs, respectively, carried the rs744373 risk-allele. Amyloid positivity was present in 23% of CNs and 51% of MCIs, whereas 2% of CNs and 35% of MCIs showed elevated [F]AV1451 binding. There was no significant effect of on voxelwise or regional [F]AV1451 in F-PACK or ADNI CNs, or in the pooled CN sample. No significant association between and [F]AV1451 was obtained in ADNI MCI patients. However, in the MCI group, numerically higher [F]AV1451 binding was observed in the risk-allele group compared to the normal group in regions corresponding to more progressed tau pathology.
We could not confirm the association between rs744373 risk-allele and elevated [F]AV1451 signal in CN older adults or MCI. Numerically higher [F]AV1451 binding was observed, however, in the MCI risk-allele group, indicating that the previously reported positive effect may be confounded by group. Therefore, when studying how the risk polymorphism influences AD pathogenesis, a distinction should be made between asymptomatic, MCI, and dementia stages of AD.
桥连整合因子1(rs744373风险多态性)与非痴呆老年人(即轻度认知障碍[MCI]加认知正常[CN]个体)中升高的[F]AV1451信号有关。然而，其与阿尔茨海默病(AD)无症状阶段的体内tau、淀粉样蛋白β(Aβ)负荷及认知障碍之间的关联仍不清楚。
在来自鲁汶大学弗拉芒预防AD队列(F-PACK)的59名认知正常(CN)参与者(39%携带载脂蛋白E[ε4])以及66名阿尔茨海默病神经影像倡议(ADNI)的CN参与者中，使用体素和区域统计方法评估rs744373对[F]AV1451结合的影响。作为对照，还对ADNI的52名MCI患者进行了研究。
F-PACK参与者中44%是rs744373风险等位基因携带者，21%显示高淀粉样蛋白负荷，8%的[F]AV1451结合升高。在ADNI中，CN和MCI参与者分别有53%和50%携带rs744373风险等位基因。23%的CN和51%的MCI存在淀粉样蛋白阳性，而2%的CN和35%的MCI显示[F]AV1451结合升高。在F-PACK或ADNI的CN参与者或合并的CN样本中，rs744373对体素或区域[F]AV1451没有显著影响。在ADNI的MCI患者中，rs744373与[F]AV1451之间未获得显著关联。然而，在MCI组中，在与更进展的tau病理学相对应的区域，rs744373风险等位基因组的[F]AV1451结合在数值上高于rs744373正常组。
我们无法证实rs744373风险等位基因与CN老年人或MCI中升高的[F]AV1451信号之间的关联。然而，在MCI的rs744373风险等位基因组中观察到[F]AV1451结合在数值上更高，这表明先前报道的阳性效应可能受组间差异的影响。因此，在研究rs744373风险多态性如何影响AD发病机制时，应区分AD的无症状、MCI和痴呆阶段。
