Kjeldsen Pernille L, Parbo Peter, Hansen Kim V, Aanerud Joel F A, Ismail Rola, Nissen Peter H, Dalby Rikke B, Damholdt Malene F, Borghammer Per, Brooks David J
Dept. of Clinical Medicine, Aarhus University, Denmark.
Dept. of Nuclear Medicine and PET, Aarhus University Hospital, Denmark.
Aging Brain. 2022 Aug 26;2:100048. doi: 10.1016/j.nbas.2022.100048. eCollection 2022.
The typical spatial pattern of amyloid-β (Aβ) in diagnosed Alzheimer's disease (AD) is that of a symmetrical hemispheric distribution. However, Aβ may be asymmetrically distributed in early stages of AD. Aβ distribution on PET has previously been explored in MCI and AD, but it has yet to be directly investigated in preclinical AD (pAD). We examined how Aβ was distributed in individuals with pAD and MCI using C-Pittsburgh Compound B (PiB) PET.
In this PET study, 79 subjects were retrospectively enrolled, including 34 controls, 24 pAD, and 21 MCI. All subjects underwent genotyping, C-PiB PET, MRI, and cognitive testing. We explored differences in Aβ load, Aβ lateralisation, and Aβ distribution, as well as associations between Aβ distribution and cognition.
The Aβ asymmetry index (AI) differed between groups, with pAD having the highest Aβ AI as compared to both controls and MCI. There was no clear Aβ lateralisation in pAD, but there was a non-significant trend towards Aβ being more left-lateralised in MCI. There were no correlations between the cognitive scores and Aβ AI or Aβ lateralisation in pAD or MCI.
The distribution of Aβ is most asymmetrical in pAD, as Aβ first starts accumulating, and it then becomes less asymmetrical in MCI, when Aβ has spread further, suggesting that more pronounced asymmetrical Aβ distribution may be a distinguishing factor in pAD. Longitudinal studies examining the distribution of Aβ across the AD continuum are needed.
在已确诊的阿尔茨海默病(AD)中,β淀粉样蛋白(Aβ)的典型空间分布模式是半球对称分布。然而,Aβ在AD早期可能呈不对称分布。此前已在轻度认知障碍(MCI)和AD中研究了PET上的Aβ分布,但尚未在临床前AD(pAD)中进行直接研究。我们使用C-匹兹堡化合物B(PiB)PET检查了pAD和MCI个体中Aβ的分布情况。
在这项PET研究中,回顾性纳入了79名受试者,包括34名对照者、24名pAD患者和21名MCI患者。所有受试者均接受基因分型、C-PiB PET、MRI和认知测试。我们探讨了Aβ负荷、Aβ偏侧化和Aβ分布的差异,以及Aβ分布与认知之间的关联。
各组之间的Aβ不对称指数(AI)不同,与对照者和MCI相比,pAD的Aβ AI最高。pAD中没有明显的Aβ偏侧化,但MCI中有Aβ更偏向左侧的非显著趋势。在pAD或MCI中,认知评分与Aβ AI或Aβ偏侧化之间没有相关性。
Aβ分布在pAD中最为不对称,因为Aβ首先开始积累,然后在MCI中变得不那么不对称,此时Aβ已经进一步扩散,这表明更明显的不对称Aβ分布可能是pAD的一个区别因素。需要进行纵向研究来检查Aβ在AD连续体中的分布情况。