Serum ferritin is a candidate biomarker of disease aggravation in amyotrophic lateral sclerosis

Yu, Jinqing; Wang, Nian; Qi, Faying; Wang, Xianjun; Zhu, Qi; Lu, Yucheng; Zhang, Huiling; Che, Fengyuan; Li, Wei

doi:10.3892/br.2018.1138

Cited by 14 publications

(19 citation statements)

References 48 publications

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“…Particularly, ALS as compared with LMND patients were characterized by increased percentages of CD3, CD4, and CD8, as already observed in ALS patients compared to healthy controls 35 , as well as higher levels of IgM. On the other hand, our classifier revealed the importance of some non-standard predictive features such as P, Cre 36 , and Tran 37 , which have been only recently indicated as factors related to the disease and potential markers and are still under study. Such data could highlight important new mechanisms related to the disease.…”

Section: Discussionsupporting

confidence: 67%

Using blood data for the differential diagnosis and prognosis of motor neuron diseases: a new dataset for machine learning applications

Greco

Chiesa

Prato

et al. 2021

Sci Rep

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Early differential diagnosis of several motor neuron diseases (MNDs) is extremely challenging due to the high number of overlapped symptoms. The routine clinical practice is based on clinical history and examination, usually accompanied by electrophysiological tests. However, although previous studies have demonstrated the involvement of altered metabolic pathways, biomarker-based monitoring tools are still far from being applied. In this study, we aim at characterizing and discriminating patients with involvement of both upper and lower motor neurons (i.e., amyotrophic lateral sclerosis (ALS) patients) from those with selective involvement of the lower motor neuron (LMND), by using blood data exclusively. To this end, in the last ten years, we built a database including 692 blood data and related clinical observations from 55 ALS and LMND patients. Each blood sample was described by 108 analytes. Starting from this outstanding number of features, we performed a characterization of the two groups of patients through statistical and classification analyses of blood data. Specifically, we implemented a support vector machine with recursive feature elimination (SVM-RFE) to automatically diagnose each patient into the ALS or LMND groups and to recognize whether they had a fast or slow disease progression. The classification strategy through the RFE algorithm also allowed us to reveal the most informative subset of blood analytes including novel potential biomarkers of MNDs. Our results show that we successfully devised subject-independent classifiers for the differential diagnosis and prognosis of ALS and LMND with remarkable average accuracy (up to 94%), using blood data exclusively.

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Section: Discussionsupporting

confidence: 67%

Using blood data for the differential diagnosis and prognosis of motor neuron diseases: a new dataset for machine learning applications

Greco

Chiesa

Prato

et al. 2021

Sci Rep

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“…These data have also important implications for studies investigating the role of iron in a more general context of neurodegenerative diseases. The pathogenetic mechanism that we described in the setting of NF might be common in various neurodegenerative disorders, such as Alzheimer (Liu et al., 2018), Parkinson (McLeary et al., 2019), and Huntington diseases (Mi et al., 2019), amyotrophic lateral sclerosis (Yu et al., 2019), and frontotemporal lobar dementia (Zhang et al., 2017), in which dysfunction of the lysosome-autophagy pathway can lead to ferritin engulfment with consequent impairment of iron homeostasis (Biasiotto et al., 2016). Accordingly, growing evidence suggests that iron imbalance is a hallmark of neurodegenerative diseases, suggesting that iron chelators may be therapeutic options for preventing these diseases (Ward et al., 2014).…”

Section: Discussionmentioning

confidence: 99%

Stem Cell Modeling of Neuroferritinopathy Reveals Iron as a Determinant of Senescence and Ferroptosis during Neuronal Aging

Cozzi¹,

Orellana²,

Santambrogio³

et al. 2019

Stem Cell Reports

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Neuroferritinopathy (NF) is a movement disorder caused by alterations in the L-ferritin gene that generate cytosolic free iron. NF is a unique pathophysiological model for determining the direct consequences of cell iron dysregulation. We established lines of induced pluripotent stem cells from fibroblasts from two NF patients and one isogenic control obtained by CRISPR/Cas9 technology. NF fibroblasts, neural progenitors, and neurons exhibited the presence of increased cytosolic iron, which was also detectable as: ferritin aggregates, alterations in the iron parameters, oxidative damage, and the onset of a senescence phenotype, particularly severe in the neurons. In this spontaneous senescence model, NF cells had impaired survival and died by ferroptosis. Thus, non-ferritin-bound iron is sufficient per se to cause both cell senescence and ferroptotic cell death in human fibroblasts and neurons. These results provide strong evidence supporting the primary role of iron in neuronal aging and degeneration.

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“…Then, 57 papers were under full-text review. Finally, 11 researches were enrolled, including five cohort studies and six cross-sectional studies (12)(13)(14)(15)(19)(20)(21)(22)(23)(24)(25). The specific process of selection is shown in Figure 1.…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

Abnormal Serum Iron-Status Indicator Changes in Amyotrophic Lateral Sclerosis (ALS) Patients: A Meta-Analysis

Wang

Chen

et al. 2020

Front. Neurol.

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Background: In recent years, the role of iron metabolism in amyotrophic lateral sclerosis (ALS) attracts more and more attention, and some studies have focused on the link between abnormal serum iron indicators and ALS. However, there are still big conflicts and inconsistency among different studies. To study the possible relationship between ALS and disturbed iron metabolism, we conducted this meta-analysis to conclude characteristics of abnormal serum iron-status indicator changes in ALS patients.Methods: We searched and screened main databases, including the PubMed, Embase, and Cochrane Library, to find studies related to the association between iron metabolism and ALS. The Revman 5.3 software was used to conduct meta-analysis.Results: Eleven studies were finally included in our analysis, composed of 1,599 ALS patients and 1,255 controls in total. The results showed that the ferritin level was much higher in ALS patients compared with controls (MD = 70.48, 95% CI [51.41, 89.55], p < 0.00001), and the transferrin level was decreased in ALS patients compared with controls (SMD = −0.28, 95% CI [−0.38, −0.18], p < 0.00001), while there was no statistical difference in iron levels (SMD = 0.48, 95% CI [−0.07, 1.03], p = 0.09) between ALS patients and controls.Conclusions: Our research finds unusual changes in several indicators representing iron status, which suggest possible iron metabolism abnormalities in ALS patients. That may provide evidence for the link between iron metabolism and the pathogenesis of ALS.

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Serum ferritin is a candidate biomarker of disease aggravation in amyotrophic lateral sclerosis

Cited by 14 publications

References 48 publications

Using blood data for the differential diagnosis and prognosis of motor neuron diseases: a new dataset for machine learning applications

Using blood data for the differential diagnosis and prognosis of motor neuron diseases: a new dataset for machine learning applications

Stem Cell Modeling of Neuroferritinopathy Reveals Iron as a Determinant of Senescence and Ferroptosis during Neuronal Aging

Abnormal Serum Iron-Status Indicator Changes in Amyotrophic Lateral Sclerosis (ALS) Patients: A Meta-Analysis

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