Current understanding of the interactions between metal ions and Apolipoprotein E in Alzheimer’s disease

Zhang, Yanhui; Gao, Huiling; Zheng, Wei; Xu, He

doi:10.1016/j.nbd.2022.105824

Cited by 16 publications

(11 citation statements)

References 231 publications

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“…61,62 In the present study, we found that children carrying the ε4 allele obtained worse scores only in the fine motor scale of the MSCA. The interaction between ApoE and metals has been investigated previously, however, mainly for essential metals such as copper, zinc, and iron; 56,63 to our knowledge, ApoE and As exposure has not been studied. The ApoE protein can bind to metals, but this ability depends on the particular isoform.…”

Section: Discussionmentioning

confidence: 99%

“…ApoE isoforms have been strongly associated with Alzheimer's pathogenesis, mainly because of their role in amyloid-beta plaque formation but also other mechanisms such as mitochondrial dysfunction and tau phosphorylation in neurons due to fragment accumulation after ApoE4 proteolysis. 55,56 The ε4 allele represents the strongest genetic risk factor for the development of late-onset Alzheimer's disease, 57 and it has also been associated with decreasing cognitive performance in adults; 58,59 however, its relationship in early life is not totally clear. In Wright's study, 60 children carrying the ε4 allele obtained better cognitive scores in the Bayley Scales of Infant and Toddler Development (BSID) evaluated at 24 months of age than noncarriers.…”

Section: Discussionmentioning

confidence: 99%

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Genetic Susceptibility to Neurotoxicity Related to Prenatal Inorganic Arsenic Exposure in Young Spanish Children

Soler-Blasco,

Llop,

Riutort-Mayol

et al. 2023

Environ. Sci. Technol.

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We explored the influence of child and maternal single nucleotide polymorphisms (SNPs) in genes related to neurological function and arsenic metabolism (i.e., ABCA1, ABCB1, PON1, CYP3A, BDNF, GSTP1, MT2A, and APOE as well as AS3MT) on the association between prenatal arsenic (As) exposure and methylation efficiency and neuropsychological development in 4–5-year-old children. Participants were 549 mother–child pairs from the INMA (Environment and Childhood) Spanish Project. We measured inorganic arsenic (iAs) and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in urine samples collected during pregnancy. Neuropsychological development was assessed at the age of 4–5 years using the McCarthy Scales of Children’s Abilities (MSCA). Several SNPs were determined in maternal and child DNA; AS3MT and APOE haplotypes were inferred. The median ∑As (sum of iAs, DMA, and MMA) was 7.08 μg/g creatinine. Statistically significant interactions for children’s APOE haplotype were observed. Specifically, ε4-carrier children had consistently lower MSCA scores in several scales with increasing ∑As and MMA concentrations. These results provide evidence regarding the neurotoxic effects of early life exposure to As, observing that the APOE ε4 allele could make children more vulnerable to this exposure.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genetic Susceptibility to Neurotoxicity Related to Prenatal Inorganic Arsenic Exposure in Young Spanish Children

Soler-Blasco,

Llop,

Riutort-Mayol

et al. 2023

Environ. Sci. Technol.

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“…Why the ApoE gene is a risk factor for both heavy metal toxicity and AD is currently unclear, and various explanations have been proposed 103,[108][109] . The previously suggested hypothesis that ApoE might bind and transport metal ions via Cys residues [100][101] , which are present in ApoE2 and ApoE3 but not in ApoE4, has recently been called into question 110 .…”

Section: Chemical Environmental and Toxicological Aspects Of Uranium ...mentioning

confidence: 99%

Characterization of uranyl (UO₂²⁺) ion binding to amyloid beta (Aβ) peptides: effects on Aβ structure and aggregation

Berntsson

Vosough

Noormägi

et al. 2023

Preprint

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Uranium (U) is naturally present in ambient air, water, and soil, and depleted uranium (DU) is released into the environment via industrial and military activities. While the radiological damage from U is rather well understood, less is known about the chemical damage mechanisms, which dominate in DU. Heavy metal exposure is associated with numerous health conditions including Alzheimers disease (AD), the most prevalent age-related cause of dementia. The pathological hallmark of AD is deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils in the brain. However, the toxic species in AD are likely oligomeric Aβ aggregates. Exposure to heavy metals such as Cd, Hg, Mn, and Pb is known to increase Aβ production, and these metals bind to Aβ peptides and modulate their aggregation. Possible effects of U in AD pathology have been sparsely studied. Here, we use biophysical techniques to study in vitro interactions between Aβ peptides and uranyl ions, UO22+, of DU. We show for the first time that uranyl ions bind to Aβ peptides with affinities in the micromolar range, induce structural changes in Aβ monomers and oligomers, and inhibit Aβ fibrillization. General toxic mechanisms of uranyl ions could be modulation of protein folding, misfolding, and aggregation.

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“…108−112 Why the ApoE gene is a risk factor for both heavy metal toxicity and AD is currently unclear, and various explanations have been proposed. 108,113,114 The previously suggested hypothesis that ApoE might bind and transport metal ions via Cys residues, 105,106 which are present in ApoE2 and ApoE3 but not in ApoE4, has recently been called into question. 115…”

Section: +mentioning

confidence: 99%

“…It therefore appears likely that the ApoE protein is involved in regulating metal homeostasis. The ApoEε4 allele is further linked to an increased probability of developing AD. − Why the ApoE gene is a risk factor for both heavy metal toxicity and AD is currently unclear, and various explanations have been proposed. ,, The previously suggested hypothesis that ApoE might bind and transport metal ions via Cys residues, , which are present in ApoE2 and ApoE3 but not in ApoE4, has recently been called into question …”

Section: Introductionmentioning

confidence: 99%

Characterization of Uranyl (UO₂²⁺) Ion Binding to Amyloid Beta (Aβ) Peptides: Effects on Aβ Structure and Aggregation

Berntsson

Vosough

Noormägi

et al. 2023

ACS Chem. Neurosci.

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Uranium (U) is naturally present in ambient air, water, and soil, and depleted uranium (DU) is released into the environment via industrial and military activities. While the radiological damage from U is rather well understood, less is known about the chemical damage mechanisms, which dominate in DU. Heavy metal exposure is associated with numerous health conditions, including Alzheimer's disease (AD), the most prevalent age-related cause of dementia. The pathological hallmark of AD is the deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils in the brain. However, the toxic species in AD are likely oligomeric Aβ aggregates. Exposure to heavy metals such as Cd, Hg, Mn, and Pb is known to increase Aβ production, and these metals bind to Aβ peptides and modulate their aggregation. The possible effects of U in AD pathology have been sparsely studied. Here, we use biophysical techniques to study in vitro interactions between Aβ peptides and uranyl ions, UO 2 2+ , of DU. We show for the first time that uranyl ions bind to Aβ peptides with affinities in the micromolar range, induce structural changes in Aβ monomers and oligomers, and inhibit Aβ fibrillization. This suggests a possible link between AD and U exposure, which could be further explored by cell, animal, and epidemiological studies. General toxic mechanisms of uranyl ions could be modulation of protein folding, misfolding, and aggregation.

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Current understanding of the interactions between metal ions and Apolipoprotein E in Alzheimer’s disease

Cited by 16 publications

References 231 publications

Genetic Susceptibility to Neurotoxicity Related to Prenatal Inorganic Arsenic Exposure in Young Spanish Children

Genetic Susceptibility to Neurotoxicity Related to Prenatal Inorganic Arsenic Exposure in Young Spanish Children

Characterization of uranyl (UO₂²⁺) ion binding to amyloid beta (Aβ) peptides: effects on Aβ structure and aggregation

Characterization of Uranyl (UO₂²⁺) Ion Binding to Amyloid Beta (Aβ) Peptides: Effects on Aβ Structure and Aggregation

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Current understanding of the interactions between metal ions and Apolipoprotein E in Alzheimer’s disease

Cited by 16 publications

References 231 publications

Genetic Susceptibility to Neurotoxicity Related to Prenatal Inorganic Arsenic Exposure in Young Spanish Children

Genetic Susceptibility to Neurotoxicity Related to Prenatal Inorganic Arsenic Exposure in Young Spanish Children

Characterization of uranyl (UO22+) ion binding to amyloid beta (Aβ) peptides: effects on Aβ structure and aggregation

Characterization of Uranyl (UO22+) Ion Binding to Amyloid Beta (Aβ) Peptides: Effects on Aβ Structure and Aggregation

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Product

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Characterization of uranyl (UO₂²⁺) ion binding to amyloid beta (Aβ) peptides: effects on Aβ structure and aggregation

Characterization of Uranyl (UO₂²⁺) Ion Binding to Amyloid Beta (Aβ) Peptides: Effects on Aβ Structure and Aggregation