磁共振成像阴性脑淀粉样血管病：脑脊液淀粉样蛋白β42 优于正电子发射断层扫描淀粉样蛋白。
Magnetic Resonance Imaging-Negative Cerebral Amyloid Angiopathy: Cerebrospinal Fluid Amyloid-β42 over Amyloid Positron Emission Tomography.
机构信息
SangYun Kim, Department of Neurology, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 13620, Republic of Korea, Tel.: +82 31 787 7462; Fax: +82 31 787 4059; E-mail:
出版信息
J Prev Alzheimers Dis. 2024;11(4):1041-1046. doi: 10.14283/jpad.2024.49.
BACKGROUND
Cerebral amyloid angiopathy (CAA) pathology is becoming increasingly important in Alzheimer's disease (AD) because of its potential link to amyloid-related imaging abnormalities, a critical side effect observed during AD immunotherapy. Identification of CAA without typical magnetic resonance imaging (MRI) markers (MRI-negative CAA) is challenging, and novel detection biomarkers are needed.
METHODS
We included 69 participants with high neuritic plaques (NP) burden, with and without CAA pathology (NP with CAA vs. NP without CAA) based on autopsy data from the Alzheimer's Disease Neuroimaging Initiative. Two participants with hemorrhagic CAA markers based on MRI were excluded and the final analysis involved 36 NP without CAA and 31 NP with CAA. A logistic regression model was used to compare the cerebrospinal fluid (CSF) amyloid-β42 (Aβ42), phosphorylated tau181, and total tau levels, the amyloid positron emission tomography (PET) standardized uptake ratio (SUVR), and cognitive profiles between NP with and without CAA. Regression models for CSF and PET were adjusted for age at death, sex, and the last assessed clinical dementia rating sum of boxes score. Models for cognitive performances was adjusted for age at death, sex, and education level.
RESULTS
NP with CAA had significantly lower CSF Aβ42 levels when compared with those without CAA (110.5 pg/mL vs. 134.5 pg/mL, p-value = 0.002). Logistic regression analysis revealed that low CSF Aβ42 levels were significantly associated with NP with CAA (odds ratio [OR]: 0.957, 95% confidence interval [CI]: 0.928, 0.987, p-value = 0.005). However, amyloid PET SUVR did not differ between NP with CAA and those without CAA (1.39 vs. 1.48, p-value = 0.666). Logistic regression model analysis did not reveal an association between amyloid PET SUVR and NP with CAA (OR: 0.360, 95% CI: 0.007, 1.741, p-value = 0.606).
CONCLUSIONS
CSF Aβ42 is more sensitive to predict MRI-negative CAA in high NP burden than amyloid PET.
背景
脑淀粉样血管病（CAA）病理学因其与淀粉样相关成像异常的潜在联系而在阿尔茨海默病（AD）中变得越来越重要，这是 AD 免疫疗法中观察到的一个关键副作用。没有典型磁共振成像（MRI）标志物的 CAA （MRI 阴性 CAA）的识别具有挑战性，需要新的检测生物标志物。
方法
我们纳入了 69 名具有高神经原纤维缠结（NP）负担的参与者，根据阿尔茨海默病神经影像学倡议的尸检数据，这些参与者有或没有 CAA 病理学（NP 伴 CAA 与 NP 不伴 CAA）。根据 MRI 排除了 2 名有出血性 CAA 标志物的参与者，最终分析涉及 36 名 NP 不伴 CAA 和 31 名 NP 伴 CAA。使用逻辑回归模型比较了脑脊液（CSF）淀粉样β42（Aβ42）、磷酸化 tau181 和总 tau 水平、淀粉样正电子发射断层扫描（PET）标准化摄取值比（SUVR）以及 NP 伴和不伴 CAA 的认知特征。CSF 和 PET 的回归模型调整了死亡时的年龄、性别和最后评估的临床痴呆评定量表总和评分。认知表现模型调整了死亡时的年龄、性别和教育水平。
结果
与 NP 不伴 CAA 相比，NP 伴 CAA 的 CSF Aβ42 水平明显降低（110.5 pg/mL 比 134.5 pg/mL，p 值=0.002）。逻辑回归分析显示，低 CSF Aβ42 水平与 NP 伴 CAA 显著相关（比值比[OR]：0.957，95%置信区间[CI]：0.928，0.987，p 值=0.005）。然而，NP 伴 CAA 与 NP 不伴 CAA 的淀粉样 PET SUVR 无差异（1.39 比 1.48，p 值=0.666）。逻辑回归模型分析未显示淀粉样 PET SUVR 与 NP 伴 CAA 之间存在关联（OR：0.360，95%CI：0.007，1.741，p 值=0.606）。
结论
与淀粉样 PET 相比，CSF Aβ42 对预测高 NP 负担的 MRI 阴性 CAA 更敏感。
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