Department of Rehabilitation, Panyu Health Management Center (Panyu Rehabilitation Hospital), Guangzhou, China.
Department of Neurology, Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Neurosci Lett. 2021 May 29;754:135765. doi: 10.1016/j.neulet.2021.135765. Epub 2021 Mar 2.
Whether the cerebrospinal fluid (CSF) biomarkers of amyloid-positive and amyloid-negative patients with mild cognitive impairment (MCI) or Alzheimer's disease (AD) are significantly different is still unknown. The purpose of this study is to compare the differences in CSF total tau, P-tau and Aβ42 in patients with amyloid-positive positron emission tomography (PET) and amyloid-negative PET, and to explore related risk factors in cognitive normal (CN), early MCI (EMCI), late MCI (LMCI) and AD. 558 participants (140 CN; 233 EMCI; 125 LMCI; 60 AD) were recruited in this study from the AD Neuroimaging Initiative (ADNI) database. The associations between CSF biomarkers were assessed by partial correlation analysis. The relations between significant variables were determined by multinomial logistic regression. Compared with amyloid-positive PET patients, patients with amyloid-negative PET had higher CSF Aβ42 and lower P-tau in the whole samples. The concentration of Aβ42 in the positive amyloid PET was significantly different in different groups, but not the negative amyloid PET (CN vs. LMCI; CN vs. AD; EMCI vs. AD, all P < 0.05). When amyloid PET was positive, a weak correlation was found between the levels of Aβ42 and P-tau only in CN group. However, a moderate degree of correlation between Aβ42 and P-tau was found in EMCI and LMCI when amyloid PET was negative. After covariates adjustment, CSF Aβ42 was significantly associated with EMCI [adjusted odds ratio (OR) = 0.99, 95 % confidence interval (CI) = 0.99-1.00, P = 0.02) and LMCI (adjusted OR = 0.99, 95 % CI = 0.99-1.00, P = 0.007)] in patients with negative amyloid PET, not in patients with positive amyloid PET. Our findings highlight that Aβ42 had strong correlations with other biomarkers and might help reduce risk of EMCI or LMCI in patients with amyloid negativity.
淀粉样蛋白阳性和淀粉样蛋白阴性的轻度认知障碍（MCI）或阿尔茨海默病（AD）患者的脑脊液（CSF）生物标志物是否存在显著差异尚不清楚。本研究旨在比较正电子发射断层扫描（PET）淀粉样蛋白阳性和阴性患者 CSF 总 tau、P-tau 和 Aβ42 的差异，并探讨认知正常（CN）、早期 MCI（EMCI）、晚期 MCI（LMCI）和 AD 患者的相关危险因素。本研究从 AD 神经影像学倡议（ADNI）数据库中招募了 558 名参与者（140 名 CN；233 名 EMCI；125 名 LMCI；60 名 AD）。采用偏相关分析评估 CSF 生物标志物之间的相关性，采用多项逻辑回归确定显著变量之间的关系。与淀粉样蛋白阳性 PET 患者相比，淀粉样蛋白阴性 PET 患者在整个样本中 CSF Aβ42 较高，P-tau 较低。阳性淀粉样 PET 组中 Aβ42 的浓度在不同组之间存在显著差异，但阴性淀粉样 PET 组无差异（CN 与 LMCI；CN 与 AD；EMCI 与 AD，均 P<0.05）。当淀粉样蛋白 PET 阳性时，仅在 CN 组中发现 Aβ42 和 P-tau 水平之间存在弱相关性。然而，当淀粉样蛋白 PET 阴性时，在 EMCI 和 LMCI 中发现 Aβ42 和 P-tau 之间存在中度相关性。调整协变量后，CSF Aβ42 与阴性淀粉样蛋白 PET 患者的 EMCI [调整后比值比（OR）=0.99，95%置信区间（CI）=0.99-1.00，P=0.02]和 LMCI [调整后 OR=0.99，95% CI=0.99-1.00，P=0.007]显著相关，而在阳性淀粉样蛋白 PET 患者中无相关性。我们的研究结果强调，Aβ42 与其他生物标志物具有很强的相关性，可能有助于降低淀粉样蛋白阴性患者发生 EMCI 或 LMCI 的风险。
