Department of Neurology, Taipei Municipal Gan-Dau Hospital, Taipei, Taiwan.
Department of Nuclear Medicine and Molecular Imaging Center, Linkou Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
Alzheimers Res Ther. 2019 Dec 27;11(1):111. doi: 10.1186/s13195-019-0566-0.
Due to the high cost and high failure rate of ascertaining amyloid positron emission tomography positivity (PET+) in patients with earlier stage Alzheimer's disease (AD), an effective pre-screening tool for amyloid PET scans is needed.
Patients with mild cognitive impairment (n = 33, 24.2% PET+, 42% females, age 74.4 ± 7.5, MMSE 26.8 ± 1.9) and mild dementia (n = 19, 63.6% PET+, 36.3% females, age 73.0 ± 9.3, MMSE 22.6 ± 2.0) were recruited. Amyloid PET imaging, Apolipoprotein E (APOE) genotyping, and plasma amyloid β (Aβ), Aβ, and total tau protein quantification by immunomagnetic reduction (IMR) method were performed. Receiver operating characteristics (ROC) analysis and Youden's index were performed to identify possible cut-off points, clinical sensitivities/specificities, and areas under the curve (AUCs).
Amyloid PET+ participants had lower plasma Aβ levels than amyloid PET-negative (PET-) subjects. APOE ε4 carriers had higher plasma Aβ than non-carriers. We developed an algorithm involving the combination of plasma Aβ and APOE genotyping. The success rate for detecting amyloid PET+ patients effectively increased from 42.3 to 70.4% among clinically suspected MCI and mild dementia patients.
Our results demonstrate the possibility of utilizing APOE genotypes in combination with plasma Aβ levels as a pre-screening tool for predicting the positivity of amyloid PET findings in early stage dementia patients.
由于在早期阿尔茨海默病（AD）患者中确定淀粉样蛋白正电子发射断层扫描阳性（PET+）的成本高且失败率高，因此需要一种有效的淀粉样蛋白 PET 扫描预筛选工具。
招募了轻度认知障碍（n=33，24.2% PET+，42%女性，年龄 74.4±7.5，MMSE 26.8±1.9）和轻度痴呆（n=19，63.6% PET+，36.3%女性，年龄 73.0±9.3，MMSE 22.6±2.0）患者。进行了淀粉样蛋白 PET 成像、载脂蛋白 E（APOE）基因分型以及通过免疫磁减少（IMR）法测定血浆淀粉样蛋白 β（Aβ）、Aβ 和总 tau 蛋白的定量。进行了接收者操作特征（ROC）分析和 Youden 指数分析，以确定可能的截断点、临床灵敏度/特异性和曲线下面积（AUCs）。
淀粉样蛋白 PET+参与者的血浆 Aβ 水平低于淀粉样蛋白 PET-（PET-）受试者。APOE ε4 携带者的血浆 Aβ 高于非携带者。我们开发了一种涉及血浆 Aβ 和 APOE 基因分型组合的算法。在临床上怀疑为 MCI 和轻度痴呆的患者中，检测淀粉样蛋白 PET+患者的成功率从 42.3%有效提高到 70.4%。
我们的结果表明，APOE 基因型与血浆 Aβ 水平结合作为预测早期痴呆患者淀粉样蛋白 PET 发现阳性的预筛选工具是可行的。
