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阿尔茨海默病患者粪便中升高的 Aβ 聚集物:概念验证研究。

Elevated Aβ aggregates in feces from Alzheimer's disease patients: a proof-of-concept study.

机构信息

Institute of Biological Information Processing, Structural Biochemistry (IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany.

attyloid GmbH, 40225, Düsseldorf, Germany.

出版信息

Alzheimers Res Ther. 2024 Oct 14;16(1):223. doi: 10.1186/s13195-024-01597-3.

Abstract

BACKGROUND

Misfolding and aggregation of amyloid β (Aβ), along with neurofibrillary tangles consisting of aggregated Tau species, are pathological hallmarks of Alzheimer's disease (AD) onset and progression. In this study, we hypothesized the clearance of Aβ aggregates from the brain and body into the gut.

METHODS

To investigate this, we used surface-based fluorescence intensity distribution analysis (sFIDA) to determine the Aβ aggregate concentrations in feces from 26 AD patients and 31 healthy controls (HC).

RESULTS

Aβ aggregates were detectable in human feces and their concentrations were elevated in AD patients compared to HC (specificity 90.3%, sensitivity 53.8%).

CONCLUSION

Thus, fecal Aβ aggregates constitute a non-invasive biomarker candidate for diagnosing AD. Whether digestion-resistant Aβ aggregates in feces are secreted via the liver and bile or directly from the enteric neuronal system remains to be elucidated.

摘要

背景

淀粉样蛋白β(Aβ)的错误折叠和聚集,以及由聚集的 Tau 物种组成的神经原纤维缠结,是阿尔茨海默病(AD)发病和进展的病理标志。在这项研究中,我们假设 Aβ 聚集体从大脑和身体清除到肠道。

方法

为了研究这一点,我们使用基于表面的荧光强度分布分析(sFIDA)来确定来自 26 名 AD 患者和 31 名健康对照者(HC)粪便中的 Aβ 聚集体浓度。

结果

Aβ 聚集体可在人类粪便中检测到,并且其浓度在 AD 患者中高于 HC(特异性 90.3%,敏感性 53.8%)。

结论

因此,粪便中的 Aβ 聚集体构成了用于诊断 AD 的非侵入性生物标志物候选物。粪便中是否存在抗消化的 Aβ 聚集体是通过肝脏和胆汁分泌的,还是直接从肠神经元系统分泌的,还有待阐明。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa7c/11472473/7ba405f24708/13195_2024_1597_Fig1_HTML.jpg

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