Alteration of Iron Concentration in Alzheimer’s Disease as a Possible Diagnostic Biomarker Unveiling Ferroptosis

Ficiarà, Eleonora; Munir, Zunaira; Boschi, Silvia; Caligiuri, Maria Eugenia; Guiot, Caterina

doi:10.3390/ijms22094479

Cited by 24 publications

(11 citation statements)

References 204 publications

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“…Indeed, while plasma and erythrocyte selenium concentrations have been reported to decrease in cognitively impaired individuals, other evidence shows that serum levels of the same mineral seem not to change in overt AD [ 170 , 184 ]. Similarly, alterations in iron, zinc, and copper have also been described [ 185 , 186 , 187 , 188 ]. For instance, Mueller et al reported that an increased serum copper/non-heme iron ratio can predict the progression from mild cognitive impairment to overt dementia, thus representing a promising early diagnostic biomarker [ 187 ].…”

Section: Resultsmentioning

confidence: 99%

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

Varesi

Carrara

Pires

et al. 2022

Cells

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Alzheimer’s Disease (AD) is a progressive neurodegenerative disease characterized by amyloid-β (Aβ) plaque deposition and neurofibrillary tangle accumulation in the brain. Although several studies have been conducted to unravel the complex and interconnected pathophysiology of AD, clinical trial failure rates have been high, and no disease-modifying therapies are presently available. Fluid biomarker discovery for AD is a rapidly expanding field of research aimed at anticipating disease diagnosis and following disease progression over time. Currently, Aβ1–42, phosphorylated tau, and total tau levels in the cerebrospinal fluid are the best-studied fluid biomarkers for AD, but the need for novel, cheap, less-invasive, easily detectable, and more-accessible markers has recently led to the search for new blood-based molecules. However, despite considerable research activity, a comprehensive and up-to-date overview of the main blood-based biomarker candidates is still lacking. In this narrative review, we discuss the role of proteins, lipids, metabolites, oxidative-stress-related molecules, and cytokines as possible disease biomarkers. Furthermore, we highlight the potential of the emerging miRNAs and long non-coding RNAs (lncRNAs) as diagnostic tools, and we briefly present the role of vitamins and gut-microbiome-related molecules as novel candidates for AD detection and monitoring, thus offering new insights into the diagnosis and progression of this devastating disease.

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Section: Resultsmentioning

confidence: 99%

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

Varesi

Carrara

Pires

et al. 2022

Cells

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“…Recently, ferroptosis, characterized by iron accumulation and lipid peroxidation, has been linked to neurodegeneration and cognitive impairment ( Dixon et al, 2012 ; Hambright et al, 2017 ). Consequently, the development of ferroptosis-based markers is gaining widespread interest, with investigations on iron chelation ( Ashraf and So, 2020 ) and potential ferroptosis-associated therapy currently underway in a range of neurodegenerative disorders, including AD ( Ficiarà et al, 2021 ). Meanwhile, increasing studies report that lncRNA plays an important role in the occurrence and development of AD ( Zhang and Li, 2021 ; Zhang and Wang, 2021 ; Zhang J. et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

lncRNA-associated ceRNA network revealing the potential regulatory roles of ferroptosis and immune infiltration in Alzheimer’s disease

Tan

Wang

Xiao

et al. 2023

Front. Aging Neurosci.

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BackgroundAlzheimer’s disease (AD) is the most common form of dementia characterized by a prominent cognitive deterioration of sufficient magnitude to impair daily living. Increasing studies indicate that non-coding RNAs (ncRNAs) are involved in ferroptosis and AD progression. However, the role of ferroptosis-related ncRNAs in AD remains unexplored.MethodsWe obtained the intersection of differentially expressed genes in GSE5281 (brain tissue expression profile of patients with AD) from the GEO database and ferroptosis-related genes (FRGs) from the ferrDb database. Least absolute shrinkage and selection operator model along with weighted gene co-expression network analysis screened for FRGs highly associated with AD.ResultsA total of five FRGs were identified and further validated in GSE29378 (area under the curve = 0.877, 95% confidence interval = 0.794–0.960). A competing endogenous RNA (ceRNA) network of ferroptosis-related hub genes (EPT1, KLHL24, LRRFIP1, CXCL2 and CD44) was subsequently constructed to explore the regulatory mechanism between hub genes, lncRNAs and miRNAs. Finally, CIBERSORT algorithms were used to unravel the immune cell infiltration landscape in AD and normal samples. M1 macrophages and mast cells were more infiltrated whereas memory B cells were less infiltrated in AD samples than in normal samples. Spearman’s correlation analysis revealed that LRRFIP1 was positively correlated with M1 macrophages (r = -0.340, P < 0.001) whereas ferroptosis-related lncRNAs were negatively correlated with immune cells, wherein miR7-3HG correlated with M1 macrophages and NIFK-AS1, EMX2OS and VAC14-AS1 correlated with memory B cells (|r| > 0.3, P < 0.001).ConclusionWe constructed a novel ferroptosis-related signature model including mRNAs, miRNAs and lncRNAs, and characterized its association with immune infiltration in AD. The model provides novel ideas for the pathologic mechanism elucidation and targeted therapy development of AD.

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“…The trafficking of iron in the brain milieu is mainly managed by the brain barrier system, with proteins, receptors, and transporters being responsible for the exchange of iron between the blood and the brain compartments [ 47 ]. The systemic organs and the brain share the same iron regulatory mechanisms and pathways based on iron-modulating proteins, providing a link to the maintenance of iron homeostasis within the brain [ 48 ].…”

Section: Where Does Brain Iron Excess Come From?mentioning

confidence: 99%

Iron Deposition in Brain: Does Aging Matter?

Ficiarà

Stura

Guiot

2022

IJMS

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The alteration of iron homeostasis related to the aging process is responsible for increased iron levels, potentially leading to oxidative cellular damage. Iron is modulated in the Central Nervous System in a very sensitive manner and an abnormal accumulation of iron in the brain has been proposed as a biomarker of neurodegeneration. However, contrasting results have been presented regarding brain iron accumulation and the potential link with other factors during aging and neurodegeneration. Such uncertainties partly depend on the fact that different techniques can be used to estimate the distribution of iron in the brain, e.g., indirect (e.g., MRI) or direct (post-mortem estimation) approaches. Furthermore, recent evidence suggests that the propensity of brain cells to accumulate excessive iron as a function of aging largely depends on their anatomical location. This review aims to collect the available data on the association between iron concentration in the brain and aging, shedding light on potential mechanisms that may be helpful in the detection of physiological neurodegeneration processes and neurodegenerative diseases such as Alzheimer’s disease.

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Alteration of Iron Concentration in Alzheimer’s Disease as a Possible Diagnostic Biomarker Unveiling Ferroptosis

Cited by 24 publications

References 204 publications

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

lncRNA-associated ceRNA network revealing the potential regulatory roles of ferroptosis and immune infiltration in Alzheimer’s disease

Iron Deposition in Brain: Does Aging Matter?

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