Cerebrospinal Fluid Erythrocyte Burden Amplifies the Impact of PTAU on Entorhinal Degeneration in Alzheimer's Disease.

IF 4.8 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Biomolecules Pub Date : 2025-09-10 DOI:10.3390/biom15091300
Rafail C Christodoulou, Georgios Vamvouras, Vasileia Petrou, Platon S Papageorgiou, Rafael Pitsillos, Ludwing Rivera, Evros Vassiliou, Sokratis G Papageorgiou, Elena E Solomou, For The Alzheimer's Disease Neuroimaging Initiative
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引用次数: 0

Abstract

Background: Alzheimer's disease (AD) involves ongoing neurodegeneration, with phosphorylated tau (PTAU) intracellular accumulation closely associated with cortical shrinking. However, not everyone with high PTAU levels shows the same degree of neurodegeneration, implying that other biological stress factors might influence tau's harmful effects. This research explores whether cerebrospinal fluid erythrocyte burden (CTRED), a marker indicating vascular-CSF barrier disruption and heme toxicity, affects the link between PTAU181 levels and entorhinal cortex atrophy in AD.

Methods: We examined 25 observations from 18 patients with AD using a linear mixed effects model. The dependent variable was entorhinal cortex volume, with fixed effects for PTAU, CTRED, and their interaction. Random intercepts accounted for variability within subjects. A cognitively normal (CN) control group was included for comparison.

Results: CTRED is significantly associated with reduced entorhinal volume (p = 0.005). A notable interaction between CTRED and PTAU was also found (p = 0.004), suggesting that higher CTRED enhances PTAU's atrophic effects. PTAU alone was not a significant predictor. No significant effects were observed in the CN group, which supports the specificity of the disease.

Conclusions: CTRED alters the neurotoxic impact of PTAU on the entorhinal cortex in AD, supporting a multi-hit model of degeneration that involves tau pathology and erythrocyte-derived stress. These findings emphasize the clinical importance of vascular-CSF biomarkers in predicting neurodegeneration and guiding targeted treatments.

脑脊液红细胞负荷放大PTAU对阿尔茨海默病内嗅变性的影响
背景:阿尔茨海默病(AD)涉及持续的神经退行性变,细胞内磷酸化tau (PTAU)积累与皮质萎缩密切相关。然而,并不是每个PTAU水平高的人都表现出相同程度的神经变性,这意味着其他生物应激因素可能会影响tau的有害作用。本研究探讨脑脊液红细胞负荷(CTRED),一个指示血管-脑脊液屏障破坏和血红素毒性的标志物,是否影响PTAU181水平与AD患者内嗅皮质萎缩之间的联系。方法:采用线性混合效应模型对18例AD患者的25项观察结果进行分析。因变量为内嗅皮质体积,对PTAU、CTRED及其相互作用有固定影响。随机截距说明了受试者内部的可变性。另设认知正常(CN)对照组进行比较。结果:CTRED与内嗅体积减少显著相关(p = 0.005)。CTRED与PTAU之间也存在显著的相互作用(p = 0.004),表明CTRED升高会增强PTAU的萎缩作用。单独的PTAU不是显著的预测因子。在CN组中未观察到明显的影响,这支持了疾病的特异性。结论:CTRED改变了PTAU对AD患者内鼻皮层的神经毒性作用,支持涉及tau病理和红细胞源性应激的多打击变性模型。这些发现强调了血管-脑脊液生物标志物在预测神经变性和指导靶向治疗方面的临床重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biomolecules
Biomolecules Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
9.40
自引率
3.60%
发文量
1640
审稿时长
18.28 days
期刊介绍: Biomolecules (ISSN 2218-273X) is an international, peer-reviewed open access journal focusing on biogenic substances and their biological functions, structures, interactions with other molecules, and their microenvironment as well as biological systems. Biomolecules publishes reviews, regular research papers and short communications.  Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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