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
{"title":"Cerebrospinal Fluid Erythrocyte Burden Amplifies the Impact of PTAU on Entorhinal Degeneration in Alzheimer's Disease.","authors":"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","doi":"10.3390/biom15091300","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>CTRED is significantly associated with reduced entorhinal volume (<i>p</i> = 0.005). A notable interaction between CTRED and PTAU was also found (<i>p</i> = 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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467901/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomolecules","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3390/biom15091300","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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.
BiomoleculesBiochemistry, 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.