Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Center for Sleep Medicine, Mayo Clinic, Rochester, MN, USA.
J Alzheimers Dis. 2022;87(4):1537-1547. doi: 10.3233/JAD-220158.
Cerebral microbleeds (CMBs) are a common vascular pathology associated with future intracerebral hemorrhage. Plasma biomarkers of amyloid, tau, and neurodegeneration may provide a screening avenue to identify those with CMBs, but evidence is conflicting.
To determine the association between plasma biomarkers (Aβ40, Aβ42, t-tau, p-tau181, p-tau217, neurofilament light chain (NfL)) and CMBs in a population-based study of aging and whether these biomarkers predict higher signal on Aβ-PET imaging in patients with multiple CMBs.
712 participants from the Mayo Clinic Study of Aging with T2* GRE MRI and plasma biomarkers were included. Biomarkers were analyzed utilizing Simoa (Aβ40, Aβ42, t-tau, NfL) or Meso Scale Discovery (p-tau181, p-tau217) platforms. Cross-sectional associations between CMBs, plasma biomarkers and Aβ-PET were evaluated using hurdle models and multivariable regression models.
Among the 188 (26%) individuals with≥1 CMB, a lower plasma Aβ42/Aβ40 ratio was associated with more CMBs after adjusting for covariables (IRR 568.5 95% CI 2.8-116,127). No other biomarkers were associated with risk or number CMBs. In 81 individuals with≥2 CMBs, higher plasma t-tau, p-tau181, and p-tau217 all were associated with higher Aβ-PET signal, with plasma p-tau217 having the strongest predictive value (r2 0.603, AIC -53.0).
Lower plasma Aβ42/Aβ40 ratio and higher plasma p-tau217 were associated with brain amyloidosis in individuals with CMBs from the general population. Our results suggest that in individuals with multiple CMBs and/or lobar intracranial hemorrhage that a lower plasma Aβ42/Aβ40 ratio or elevated p-tau217 may indicate underlying cerebral amyloid angiopathy.
脑微出血（CMBs）是一种与未来颅内出血相关的常见血管病理学。淀粉样蛋白、tau 和神经退行性变的血浆生物标志物可能为识别 CMBs 提供一种筛查途径，但证据存在矛盾。
在一项基于人群的老龄化研究中，确定血浆生物标志物（Aβ40、Aβ42、t-tau、p-tau181、p-tau217、神经丝轻链（NfL））与 CMBs 之间的关联，以及这些生物标志物是否可预测多发性 CMBs 患者的 Aβ-PET 成像中更高的信号。
纳入了 Mayo 诊所老龄化研究中的 712 名具有 T2* GRE MRI 和血浆生物标志物的参与者。利用 Simoa（Aβ40、Aβ42、t-tau、NfL）或 Meso Scale Discovery（p-tau181、p-tau217）平台分析生物标志物。使用障碍模型和多变量回归模型评估 CMBs、血浆生物标志物和 Aβ-PET 之间的横断面关联。
在 188 名（26%）存在≥1 个 CMB 的个体中，在校正协变量后，较低的血浆 Aβ42/Aβ40 比值与更多的 CMB 相关（IRR 568.5 95%CI 2.8-116,127）。其他生物标志物与风险或 CMB 数量均无关联。在 81 名存在≥2 个 CMB 的个体中，较高的血浆 t-tau、p-tau181 和 p-tau217 均与 Aβ-PET 信号较高相关，其中血浆 p-tau217 具有最强的预测价值（r2 0.603，AIC -53.0）。
在来自普通人群的 CMB 个体中，较低的血浆 Aβ42/Aβ40 比值和较高的血浆 p-tau217 与脑淀粉样蛋白沉积有关。我们的结果表明，在存在多发性 CMB 和/或脑叶颅内出血的个体中，较低的血浆 Aβ42/Aβ40 比值或升高的 p-tau217 可能表明存在脑淀粉样血管病。
