Translational and Cli nical Research Institute, Newcastle University, UK.
Translational and Cli nical Research Institute, Newcastle University, UK.
Parkinsonism Relat Disord. 2022 Aug;101:111-116. doi: 10.1016/j.parkreldis.2022.07.008. Epub 2022 Jul 19.
Amyloid-β (Aβ) deposition is common in dementia with Lewy bodies (DLB) and has been associated with more rapid disease progression. An effective biomarker that identified the presence of significant brain Aβ in people with DLB may be useful to identify and stratify participants for research studies and to inform prognosis in clinical practice. Plasma biomarkers are emerging as candidates to fulfil this role.
Thirty-two participants with DLB had brain amyloid (18F-florbetapir) PET, of whom 27 also had an MRI to enable the calculation of 18F-florbetapir SUVR. Plasma Aβ42/40, phosphorylated tau (p-tau181), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) were measured using single molecule array (Simoa). The plasma biomarkers were investigated for correlation with 18F-florbetapir SUVR, discriminant ability to identify Aβ-positive cases based on a predefined SUVR threshold of 1.10 and correlation with subsequent cognitive decline over one year.
All four plasma markers significantly correlated with 18F-florbetapir SUVR (|β| = 0.40-0.49; p < .05). NfL had the greatest area under the receiver operating characteristic curve to identify Aβ-positive cases (AUROC 0.84 (95% CI 0.66, 1); β = 0.46, p = .001), whereas Aβ42/40 had the smallest (AUROC 0.73 (95% CI 0.52, 0.95); β = -0.47, p = .01). Accuracy was highest when combining all four biomarkers (AUROC 0.92 (95% CI 0.80, 1)). Lower plasma Aβ42/40 was significantly associated with more rapid decline in cognition (β = 0.53, p < .01).
Plasma biomarkers have the potential to identify Aβ deposition in DLB. Further work in other cohorts is required to determine and validate optimal cut-offs for these biomarkers.
淀粉样蛋白-β（Aβ）沉积在路易体痴呆（DLB）中很常见，并且与疾病的快速进展有关。一种有效的生物标志物，能够识别出 DLB 患者大脑中存在大量 Aβ，可能有助于识别和分层研究参与者，并为临床实践提供预后信息。血浆生物标志物正在成为满足这一需求的候选者。
32 名 DLB 患者进行了脑淀粉样蛋白（18F-florbetapir）PET 检查，其中 27 名患者还进行了 MRI 检查，以计算 18F-florbetapir SUVR。使用单分子阵列（Simoa）测量血浆 Aβ42/40、磷酸化 tau（p-tau181）、神经胶质纤维酸性蛋白（GFAP）和神经丝轻链（NfL）。研究了这些血浆生物标志物与 18F-florbetapir SUVR 的相关性、基于预定 SUVR 阈值（1.10）识别 Aβ 阳性病例的判别能力以及与随后一年认知能力下降的相关性。
所有四种血浆标志物均与 18F-florbetapir SUVR 显著相关（|β|=0.40-0.49；p<0.05）。NfL 对识别 Aβ 阳性病例的受试者工作特征曲线下面积最大（AUROC 0.84（95%CI 0.66，1）；β=0.46，p=0.001），而 Aβ42/40 最小（AUROC 0.73（95%CI 0.52，0.95）；β=-0.47，p=0.01）。当联合使用所有四种生物标志物时，准确性最高（AUROC 0.92（95%CI 0.80，1））。较低的血浆 Aβ42/40 与认知能力下降更快显著相关（β=0.53，p<0.01）。
血浆生物标志物有可能识别 DLB 中的 Aβ 沉积。需要在其他队列中进行进一步的研究，以确定和验证这些生物标志物的最佳截断值。
