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

IF 7.9 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's Research & Therapy Pub Date : 2024-10-14 DOI:10.1186/s13195-024-01597-3

Marlene Pils, Alexandra Dybala, Anja Schaffrath, Fabian Rehn, Janine Kutzsche, Lara Blömeke, Markus Tusche, Pelin Özdüzenciler, Tuyen Bujnicki, Victoria Kraemer-Schulien, Hannes Gramespacher, Maximilian H T Schmieschek, Michael T Barbe, Oezguer A Onur, Gereon R Fink, Gültekin Tamgüney, Oliver Bannach, Dieter Willbold

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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.

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阿尔茨海默病患者粪便中 Aβ 聚集物的升高：概念验证研究。

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 聚集物会从大脑和身体清除到肠道：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）测定了26名AD患者和31名健康对照者（HC）粪便中Aβ聚集体的浓度：结果：在人类粪便中可检测到 Aβ 聚集物，与 HC 相比，AD 患者的 Aβ 聚集物浓度更高（特异性 90.3%，灵敏度 53.8%）：因此，粪便中的Aβ聚集物是诊断AD的一种非侵入性生物标志物。粪便中的抗消化Aβ聚集物是通过肝脏和胆汁分泌的，还是直接从肠道神经元系统分泌的，还有待进一步研究。

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来源期刊

Alzheimer's Research & Therapy 医学-神经病学

CiteScore

13.10

自引率

3.30%

发文量

172

审稿时长

>12 weeks

期刊介绍： Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.