Division of Biomedical Statistics and Informatics, Mayo Clinic and Foundation, Rochester, MN, USA.
Alzheimers Dement. 2011 Mar;7(2):133-41. doi: 10.1016/j.jalz.2010.08.230. Epub 2011 Feb 1.
Positron-emission tomography (PET) imaging of amyloid with Pittsburgh Compound B (PIB) and Aβ42 levels in the cerebrospinal fluid (CSF Aβ42) demonstrate a highly significant inverse correlation. Both these techniques are presumed to measure brain Aβ amyloid load. The objectives of this study were to develop a method to transform CSF Aβ42 measures into calculated PIB measures (PIBcalc) of Aβ amyloid load, and to partially validate the method in an independent sample of subjects.
In all, 41 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent PIB PET imaging and lumbar puncture (LP) at the same time. This sample, referred to as the "training" sample (nine cognitively normal subjects, 22 subjects with mild cognitive impairment, and 10 subjects with Alzheimer's disease), was used to develop a regression model by which CSF Aβ42 (with apolipoprotein E ɛ4 carrier status as a covariate) was transformed into units of PIB PET (PIBcalc). An independent "supporting" sample of 362 ADNI subjects (105 cognitively normal subjects, 164 subjects with mild cognitive impairment, and 93 subjects with Alzheimer's disease) who underwent LP but not PIB PET imaging had their CSF Aβ42 values converted to PIBcalc. These values were compared with the overall PIB PET distribution found in the ADNI subjects (n=102).
A linear regression model demonstrates good prediction of actual PIB PET from CSF Aβ42 measures obtained in the training sample (R(2)=0.77, P<.001). PIBcalc data (derived from CSF Aβ42) in the supporting sample of 362 ADNI subjects who underwent LP but not PIB PET imaging demonstrate group-wise distributions that are highly consistent with the larger ADNI PIB PET distribution and with published PIB PET imaging studies.
Although the precise parameters of this model are specific for the ADNI sample, we conclude that CSF Aβ42 can be transformed into PIBcalc measures of Aβ amyloid load. Brain Aβ amyloid load can be ascertained at baseline in therapeutic or observational studies by either CSF or amyloid PET imaging and the data can be pooled using well-established multiple imputation techniques that account for the uncertainty in a CSF-based PIBcalc value.
正电子发射断层扫描（PET）成像与匹兹堡化合物 B（PIB）和脑脊液（CSF Aβ42）中的 Aβ42 水平显示出高度显著的反比相关。这两种技术都被认为可以测量大脑中的 Aβ淀粉样蛋白负荷。本研究的目的是开发一种将 CSF Aβ42 测量值转换为 Aβ 淀粉样蛋白负荷的计算 PIB 测量值（PIBcalc）的方法，并在独立的受试者样本中对该方法进行部分验证。
共有 41 名来自阿尔茨海默病神经影像学倡议（ADNI）的受试者同时接受了 PIB PET 成像和腰椎穿刺（LP）。这个样本，称为“训练”样本（九名认知正常的受试者、22 名轻度认知障碍的受试者和 10 名阿尔茨海默病的受试者），用于通过回归模型将 CSF Aβ42（载脂蛋白 E ɛ4 携带者状态作为协变量）转化为 PIB PET 的单位（PIBcalc）。362 名 ADNI 受试者的独立“支持”样本（105 名认知正常的受试者、164 名轻度认知障碍的受试者和 93 名阿尔茨海默病的受试者）接受了 LP 但未接受 PIB PET 成像，他们的 CSF Aβ42 值被转换为 PIBcalc。这些值与 ADNI 受试者中发现的总体 PIB PET 分布进行了比较（n=102）。
线性回归模型显示，从训练样本中获得的 CSF Aβ42 测量值可以很好地预测实际的 PIB PET（R²=0.77，P<.001）。在接受 LP 但未接受 PIB PET 成像的 362 名 ADNI 受试者的支持样本中，PIBcalc 数据（来自 CSF Aβ42）的组间分布与 ADNI 的 PIB PET 分布以及已发表的 PIB PET 成像研究高度一致。
尽管该模型的精确参数是特定于 ADNI 样本的，但我们得出结论，CSF Aβ42 可以转换为 Aβ 淀粉样蛋白负荷的 PIBcalc 测量值。通过 CSF 或淀粉样蛋白 PET 成像，可以在治疗或观察性研究中在基线时确定脑 Aβ 淀粉样蛋白负荷，并且可以使用经过充分验证的多重插补技术来汇总数据，这些技术可以考虑到 CSF 基础 PIBcalc 值的不确定性。
