Effective litmus gene test for monitoring the quality of blood samples: Application to Alzheimer’s disease diagnostics

Shim, Sung Mi; Kim, Jong Hoon; Jeon, Jae‐Pil

doi:10.1038/s41598-017-17293-2

Cited by 6 publications

(4 citation statements)

References 36 publications

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“…In our research, we found that CCL20 acts as a protective factor against AD [51]. It has been reported that plasma from AD patients can inhibit the generation of CCL20 in vitro [52]. Additionally, the expression of CCL20 has been found to decrease in the plasma of AD mouse models [53].…”

Section: Discussionsupporting

confidence: 58%

Novel Plasma Protein Biomarkers: A Time-Dependent predictive model for Alzheimer's Disease

Zhuang,

Yang,

Ren

et al. 2023

Preprint

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Background The accurate prediction of Alzheimer's disease (AD) is crucial for the efficient management of its progression. The objective of this research is to construct a new risk predictive model utilizing novel plasma protein biomarkers for predicting AD incidence in the future and analyze their potential biological correlation with AD incidence. Methods A cohort of 440 participants aged 60 years and older from the Alzheimer's Disease Neuroimaging Initiative (ADNI) longitudinal cohort was utilized. The baseline plasma proteomics data was employed to conduct Cox regression, LASSO regression, and cross-validation to identify plasma protein signatures predictive of AD risk. Subsequently, a multivariable Cox proportional hazards model based on these signatures was constructed. The performance of the risk prediction model was evaluated using time-dependent receiver operating characteristic (t-ROC) curves and Kaplan-Meier curves. Additionally, we analyzed the correlations between protein signature expression in plasma and predicted AD risk, the time of AD onset, the expression of protein signatures in cerebrospinal fluid (CSF), the expression of CSF biomarkers, and APOE ε4 genotypes. Results We identified seven protein signatures (APOE, CGA, CRP, CCL26, CCL20, NRCAM, and PYY) that independently predicted AD incidence in the future. The risk prediction model demonstrated area under the ROC curve (AUC) values of 0.77, 0.76, and 0.77 for predicting AD incidence at 4, 6, and 8 years, respectively. Furthermore, the model remained stable in the range of the 3rd to the 12th year (ROC ≥ 0.75). The low-risk group, as defined by the model, exhibited a significantly later AD onset compared to the high-risk group (P < 0.0001). Moreover, all protein signatures exhibited significant correlations with AD risk (P < 0.001) and the time of AD onset (P < 0.01). There was no strong correlation between the protein expression levels in plasma and CSF, as well as AD CSF biomarkers. APOE, CGA, and CRP exhibited significantly lower expression levels in APOE ε4 positive individuals (P < 0.05). Conclusion Our research has successfully identified protein signatures in plasma as potential risk biomarkers that can independently predict AD incidence in the future. Notably, this risk prediction model has demonstrated commendable predictive performance and stability over time. These findings underscore the promising utility of plasma protein signatures in dynamically predicting the risk of Alzheimer's disease, thereby facilitating early screening and intervention strategies.

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Section: Discussionsupporting

confidence: 58%

Novel Plasma Protein Biomarkers: A Time-Dependent predictive model for Alzheimer's Disease

Zhuang,

Yang,

Ren

et al. 2023

Preprint

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“…The NF-κB pathway mediates the transcription of MIP-3α [27]. It has been reported that AD patients' plasma can suppress the generation of CCL20 in SHSY-5Y cell lines [28]. This suggests that there factors may influence the NF-κB pathway and induce immunologic abnormalities in the peripheral system in the development of tau pathology.…”

Section: Discussionmentioning

confidence: 99%

The behavioural and neuropathologic sexual dimorphism and absence of MIP-3α in tau P301S mouse model of Alzheimer’s disease

Sun

Guo

Feng

et al. 2020

J Neuroinflammation

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Background: Tau hyper-phosphorylation has been considered a major contributor to neurodegeneration in Alzheimer's disease (AD) and related tauopathies, and has gained prominence in therapeutic development for AD. To elucidate the pathogenic mechanisms underlying AD and evaluate therapeutic approaches targeting tau, numerous transgenic mouse models that recapitulate critical AD-like pathology have been developed. Tau P301S transgenic mice is one of the most widely used mouse models in AD research. Extensive studies have demonstrated that sex significantly influences AD pathology, behavioral status, and therapeutic outcomes, suggesting that studies using mouse models of AD must consider sex-and age-related differences in neuropathology, behavior, and plasma content. Method: We systematically investigated differences in tau P301S transgenic mice (PS19 line) and wildtype littermates of different sex behavioral performance, tau neuropathology, and biomarkers in plasma and brain. Results: Male P301S transgenic mice exhibited significant changes in weight loss, survival rate, clasping, kyphosis, composite phenotype assessment, nest building performance, tau phosphorylation at Ser202/Thr205, and astrocyte activation compared to that of wild-type littermates. In contrast, female P301S transgenic mice were only sensitive in the Morris water maze and open field test. In addition, we characterized the absence of macrophage-inflammatory protein (MIP-3α) and the upregulation of interferon (IFN)-γ, interleukin (IL)-5, and IL-6 in the plasma of P301S transgenic mice, which can be served as potential plasma biomarkers in P301S Tg mice. Male P301S transgenic mice expressed more monokine induced by IFN-γ (MIG), tumor necrosis factor-α (TNF-α), IL-10, and IL-13 than those of female P301S mice. Conclusion: Our findings highlight sexual dimorphism in the behavior, neuropathology, and plasma proteins in tau P301S transgenic AD mice, indicating that the use of male P301S transgenic mice may be more suitable for assessing anti-phosphorylated tau therapeutic strategies for AD and related tauopathies, and the MIP-3α may be a new potential plasma biomarker.

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“…MIP-3α is a chemokine for immature dendritic cells. The NF-κB pathway mediates the transcription of MIP-3α [27].It has been reported that AD patients' plasma can suppress the generation of CCL20 in SHSY-5Y cell lines [28]. This suggests there factors may influence the NF-κB pathway and induce immunologic abnormalities in the peripheral system in the development of tau pathology.…”

Section: Discussionmentioning

confidence: 99%

The behavioural and neuropathologic sexual dimorphism and absence of MIP-3α in tau P301S mouse model of Alzheimer’s disease

Sun

Guo

Feng

et al. 2020

Preprint

View full text Add to dashboard Cite

Background : Tau hyper-phosphorylation has been considered a major contributor to neurodegeneration in Alzheimer’s disease (AD) and related tauopathies, and has gained prominence in therapeutic development for AD. To elucidate the pathogenic mechanisms underlying AD and evaluate therapeutic approaches targeting tau, numerous transgenic mouse models that recapitulate critical AD-like pathology have been developed. Tau P301S transgenic mice is one of the most widely used mouse models in AD research. Extensive studies have demonstrated that sex significantly influences AD pathology, behavioral status and therapeutic outcomes, suggesting that studies using mouse models of AD must consider sex- and age-related differences in neuropathology, behavior, and plasma content. Method : We systematically investigated differences in tau P301S transgenic mice (PS19 line) and wildtype littermates of different sex behavioral performance, tau neuropathology and biomarkers in plasma and brain. Results : Male P301S transgenic mice exhibited significant changes in weight loss, survival rate, clasping, kyphosis, composite phenotype assessment, nest building performance, tau phosphorylation at Ser202/Thr205 and astrocyte activation compared to that of wild type littermates. In contrast, female P301S transgenic mice were only sensitive in the Morris Water Maze and open field test. In addition, we characterized the absence of macrophage-inflammatory protein (MIP-3α) and the upregulation of interferon (IFN)-γ, interleukin (IL)-5, and IL-6 in the plasma of P301S transgenic mice, which can be served as potential plasma biomarkers in P301S Tg mice. Male P301S transgenic mice expressed more monokine induced by IFN-γ (MIG), tumor necrosis factor-α (TNF-α), IL-10 and IL-13 than those of female P301S mice. Conclusion : Our findings highlight sexual dimorphism in the behavior, neuropathology, and plasma proteins in tau P301S transgenic AD mice, indicating that the use of male P301S transgenic mice may be more suitable for assessing anti-phosphorylated tau therapeutic strategies for AD and related tauopathies, and the MIP-3α may be a new potential plasma biomarker.

show abstract

Effective litmus gene test for monitoring the quality of blood samples: Application to Alzheimer’s disease diagnostics

Cited by 6 publications

References 36 publications

Novel Plasma Protein Biomarkers: A Time-Dependent predictive model for Alzheimer's Disease

Novel Plasma Protein Biomarkers: A Time-Dependent predictive model for Alzheimer's Disease

The behavioural and neuropathologic sexual dimorphism and absence of MIP-3α in tau P301S mouse model of Alzheimer’s disease

The behavioural and neuropathologic sexual dimorphism and absence of MIP-3α in tau P301S mouse model of Alzheimer’s disease

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