José Luis Molinuevo, Alzheimer Prevention Program - Barcelonaβeta Brain Research Center, Wellington 30, 08005, Barcelona, Spain, +34933160990, E-mail:
J Prev Alzheimers Dis. 2021;8(1):68-77. doi: 10.14283/jpad.2020.51.
Amyloid-β (Aβ) positivity is defined using different biomarkers and different criteria. Criteria used in symptomatic patients may conceal meaningful early Aβ pathology in preclinical Alzheimer. Therefore, the description of sensitive cutoffs to study the pathophysiological changes in early stages of the Alzheimer's continuum is critical. Here, we compare different Aβ classification approaches and we show their performance in detecting pathophysiological changes downstream Aβ pathology. We studied 368 cognitively unimpaired individuals of the ALFA+ study, many of whom in the preclinical stage of the Alzheimer's continuum. Participants underwent Aβ PET and CSF biomarkers assessment. We classified participants as Aβ -positive using five approaches: (1) CSF Aβ42 < 1098 pg/ml; (2) CSF Aβ42/40 < 0.071; (3) Aβ PET Centiloid > 12; (4) Aβ PET Centiloid > 30 or (5) Aβ PET Positive visual read. We assessed the correlations between Aβ biomarkers and compared the prevalence of Aβ positivity. We determined which approach significantly detected associations between Aβ pathology and tau/neurodegeneration CSF biomarkers. We found that CSF-based approaches result in a higher Aβ-positive prevalence than PET-based ones. There was a higher number of discordant participants classified as CSF Aβ-positive but PET Aβ-negative than CSF Aβ-negative but PET Aβ-positive. The CSF Aβ 42/40 approach allowed optimal detection of significant associations with CSF p-tau and t-tau in the Aβ-positive group. Altogether, we highlight the need for sensitive Aβ -classifications to study the preclinical Alzheimer's continuum. Approaches that define Aβ positivity based on optimal discrimination of symptomatic Alzheimer's disease patients may be suboptimal for the detection of early pathophysiological alterations in preclinical Alzheimer.
淀粉样蛋白-β（Aβ）阳性的定义使用了不同的生物标志物和不同的标准。在有症状的患者中使用的标准可能会掩盖阿尔茨海默病临床前阶段有意义的早期 Aβ 病理学。因此，描述用于研究阿尔茨海默病连续体早期阶段病理生理变化的敏感截止值至关重要。在这里，我们比较了不同的 Aβ 分类方法，并展示了它们在检测 Aβ 病理学下游病理生理变化中的性能。我们研究了来自 ALFA+研究的 368 名认知正常的个体，其中许多人处于阿尔茨海默病连续体的临床前阶段。参与者接受了 Aβ PET 和 CSF 生物标志物评估。我们使用以下五种方法将参与者分类为 Aβ 阳性：（1）CSF Aβ42<1098pg/ml；（2）CSF Aβ42/40<0.071；（3）Aβ PET Centiloid>12；（4）Aβ PET Centiloid>30 或（5）Aβ PET 阳性视觉读取。我们评估了 Aβ 生物标志物之间的相关性，并比较了 Aβ 阳性的患病率。我们确定了哪种方法可以显著检测出 Aβ 病理学与 tau/神经退行性变 CSF 生物标志物之间的关联。我们发现基于 CSF 的方法比基于 PET 的方法导致更高的 Aβ 阳性患病率。有更多的不一致参与者被归类为 CSF Aβ 阳性但 PET Aβ 阴性，而不是 CSF Aβ 阴性但 PET Aβ 阳性。CSF Aβ42/40 方法允许在 Aβ 阳性组中最佳检测与 CSF p-tau 和 t-tau 的显著相关性。总之，我们强调需要使用敏感的 Aβ 分类方法来研究临床前阿尔茨海默病连续体。基于最佳区分有症状的阿尔茨海默病患者来定义 Aβ 阳性的方法可能不适用于检测临床前阿尔茨海默病的早期病理生理改变。
