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脑啡肽酶 1 和其他与阿尔茨海默病相关的生物标志物在脑脊液和血浆中的差异可区分阿尔茨海默病患者和认知障碍神经梅毒患者。

BACE1 and Other Alzheimer's-Related Biomarkers in Cerebrospinal Fluid and Plasma Distinguish Alzheimer's Disease Patients from Cognitively-Impaired Neurosyphilis Patients.

机构信息

Department of Neurology, the Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.

Department of Geriatric Psychiatry, the Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.

出版信息

J Alzheimers Dis. 2020;77(1):313-322. doi: 10.3233/JAD-200362.

Abstract

BACKGROUND

Patients with spirochetal infection, which causes neurosyphilis (NS) and at a later stage general paresis of the insane (GPI), present with brain pathology features of Alzheimer's disease (AD). However, the relationships among these illnesses regarding biomarker levels are still unclear.

OBJECTIVE

To explore biomarker levels in NS and GPI compared with those in AD and the relationship between biomarker levels and cognitive function in NS and GPI.

METHODS

Levels of neurogranin (NGRN) and β-amyloid precursor protein cleaving enzyme (BACE1) in cerebrospinal fluid (CSF)/plasma, together with amyloid-β 1-40 (Aβ40), Aβ42, and total tau in the CSF of 23 AD patients, 55 GPI patients, and 13 NS patients were measured. Patients were classified into none-to-mild, moderate, and severe stages of cognitive impairment.

RESULTS

Levels of CSF NGRN, BACE1, and tau as well as plasma BACE1 levels were significantly different among groups. In the none-to-mild stage, plasma BACE1 levels correlated with the protein levels in CSF and were significantly increased in AD patients versus GPI patients. The CSF tau levels in AD patients were significantly increased versus GPI patients in the moderate and severe stages. Pooling data from GPI and NS patients, both CSF tau and plasma NGRN levels correlated with cognitive scale scores.

CONCLUSION

GPI and NS patients might have different biomarker level patterns compared to AD patients. While plasma BACE1 could be a promising early biomarker for distinguishing AD from GPI, CSF tau and plasma NGRN levels might be valuable in indications of cognitive function in pooled NS populations.

摘要

背景

螺旋体感染可引起神经梅毒(NS),进而在后期导致麻痹性痴呆(GPI),其脑部病理学特征与阿尔茨海默病(AD)相似。然而,这些疾病在生物标志物水平方面的关系仍不清楚。

目的

探讨 NS 和 GPI 与 AD 相比的生物标志物水平,以及 NS 和 GPI 中生物标志物水平与认知功能的关系。

方法

测量了 23 例 AD 患者、55 例 GPI 患者和 13 例 NS 患者脑脊液(CSF)/血浆中的神经颗粒蛋白(NGRN)和β-淀粉样前体蛋白裂解酶(BACE1)水平,以及 CSF 中的淀粉样蛋白-β 1-40(Aβ40)、Aβ42 和总tau。将患者分为无至轻度、中度和重度认知障碍阶段。

结果

CSF NGRN、BACE1 和 tau 以及血浆 BACE1 水平在各组之间存在显著差异。在无至轻度阶段,与 CSF 中的蛋白水平相比,血浆 BACE1 水平与 AD 患者和 GPI 患者的水平相关,且 AD 患者的血浆 BACE1 水平显著高于 GPI 患者。在中重度阶段,AD 患者的 CSF tau 水平明显高于 GPI 患者。汇总 GPI 和 NS 患者的数据,CSF tau 和血浆 NGRN 水平与认知量表评分相关。

结论

与 AD 患者相比,GPI 和 NS 患者可能具有不同的生物标志物水平模式。虽然血浆 BACE1 可能是区分 AD 与 GPI 的有前途的早期生物标志物,但 CSF tau 和血浆 NGRN 水平可能对合并 NS 人群的认知功能有价值。

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