Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
Knight Initiative for Brain Resilience, Stanford University, Stanford, California, USA.
Ann Clin Transl Neurol. 2024 May;11(5):1197-1210. doi: 10.1002/acn3.52034. Epub 2024 Mar 4.
More than half of neurodegenerative disease patients have multiple pathologies at autopsy; however, most receive one diagnosis during life. We used the α-synuclein seed amplification assay (αSyn-SAA) and CSF biomarkers for amyloidosis and Alzheimer's disease (AD) neuropathological change (ADNC) to determine the frequency of co-pathologies in participants clinically diagnosed with Lewy body (LB) disease or AD.
Using receiver operating characteristic analyses on retrospective CSF samples from 150 participants determined αSyn-SAA accuracy, sensitivity, and specificity for identifying clinically defined LB disease and predicting future change in clinical diagnosis. CSF biomarkers helped determine the frequency of concomitant Lewy body pathology, ADNC, and/or amyloidosis in participants with LB disease and AD, across clinical spectra.
Following a decade-long follow-up, the clinically or autopsy-defined diagnosis changed for nine participants. αSyn-SAA demonstrated improved accuracy (91.3%), sensitivity (89.3%), and specificity (93.3%) for identifying LB disease compared to all non-LB disease, highlighting the limitations of clinical diagnosis alone. When examining biomarkers of co-pathology, amyloidosis was present in 18%, 48%, and 71% (χ(2) = 13.56, p = 0.001) and AD biomarkers were present in 0%, 8.7%, and 42.9% (χ(2) = 18.44, p < 0.001) of LB disease participants with different stages of cognitive impairment respectively. Co-occurring biomarkers for αSyn-SAA and amyloidosis were present in 12% and 14% of AD compared to 43% and 57% LB disease participants with different stages of cognitive impairment (χ(3) = 13.87, p = 0.003).
Our study shows that using a combination of αSyn-SAA and AD biomarkers can identify people with αSyn, ADNC, and co-pathology better and earlier than traditional clinical diagnostic criteria alone.
尸检显示超过一半的神经退行性疾病患者有多种病变，但大多数患者在生前仅被诊断出一种疾病。我们使用α-突触核蛋白种子扩增检测（αSyn-SAA）和脑脊液生物标志物来检测淀粉样变性和阿尔茨海默病（AD）神经病变（ADNC），以确定临床上诊断为路易体（LB）病或 AD 的患者中合并疾病的频率。
使用回顾性脑脊液样本对 150 名参与者进行接收器操作特征分析，以确定 αSyn-SAA 对识别临床上定义的 LB 病和预测未来临床诊断变化的准确性、敏感性和特异性。脑脊液生物标志物有助于确定 LB 病和 AD 患者中伴有路易体病理、ADNC 和/或淀粉样变性的频率，跨越临床谱。
经过十年的随访，9 名参与者的临床或尸检诊断发生了变化。与所有非 LB 疾病相比，αSyn-SAA 对 LB 病的识别具有更高的准确性（91.3%）、敏感性（89.3%）和特异性（93.3%），突出了单独临床诊断的局限性。当检查合并疾病的生物标志物时，淀粉样变性分别存在于 18%、48%和 71%（χ(2) = 13.56，p = 0.001），AD 生物标志物分别存在于 0%、8.7%和 42.9%（χ(2) = 18.44，p < 0.001）的 LB 病患者，认知障碍的不同阶段。在不同认知障碍阶段的 AD 患者中，αSyn-SAA 和淀粉样变性的共存生物标志物分别为 12%和 14%，而 LB 病患者分别为 43%和 57%（χ(3) = 13.87，p = 0.003）。
我们的研究表明，使用 αSyn-SAA 和 AD 生物标志物的组合可以比传统的临床诊断标准更早地更好地识别出具有 αSyn、ADNC 和合并疾病的人。
