Serum Non-Ceruloplasmin Non-Albumin Copper Elevation in Mild Cognitive Impairment and Dementia due to Alzheimer’s Disease: A Case Control Study

Rozzini, Luca; Lanfranchi, Francesco; Padovani, Alessandro; Catalani, Simona; Gilberti, Maria Enrica; Paganelli, Matteo; Apostoli, Pietro; Padovani, Alessandro

doi:10.3233/jad-170552

Cited by 25 publications

(15 citation statements)

References 34 publications

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“…Several studies have indicated that the CP in the AD patients may be used as the new hallmarks in the serum [41]. Another ferric oxidase protein, HEPH, presents homology with CP, both of which participates in iron metabolism.…”

Section: Discussionmentioning

confidence: 99%

Active compounds of herbs ameliorate impaired cognition in APP/PS1 mouse model of Alzheimer’s disease

Shao³

et al. 2019

Aging

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Alzheimer’s disease (AD), the most common cause of dementia, is a neurodegenerative disorder characterized by amyloid plaque accumulations, intracellular tangles and neuronal loss in certain brain regions. It has been shown that a disturbance of normal iron metabolism contributes to the pathophysiology of AD. However, the mechanism underlying abnormal iron load in the brain of AD patients is unclear. The frontal cortex, an important brain structure for executive function, is one of the regions affected by AD. We investigated the beneficial effects of active compounds of Epimedium, Astragaoside and Puerarin on iron metabolism in the frontal cortex of six-month-old APPswe/PS1ΔE9 (APP/PS1) double transgenic mouse, a model of AD. Treatment with the active compounds reduced cognitive and memory deficits and damaged cell ultrastructure in APP/PS1 mice. These beneficial effects were associated with changes in expression levels of iron metabolism proteins in the frontal cortex, including divalent metal transporter with iron response element (DMT1-with IRE), divalent metal transporter without iron response element (DMT1-without IRE), transferrin (TF) and transferring receptor 1 (TfR1); three release proteins including the exporter ferroportin 1 (Fpn1), ceruloplasmin (CP) and hephaestin (HEPH), one increased storage iron protein ferritin and one iron regulating hormone hepcidin. These findings suggest that the active compounds improve cognition and memory in brain neurodegenerative disorders and these beneficial effects are associated with reduced impairment of iron metabolism. This study may provide a new strategy for developing novel drugs to treat AD.

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Section: Discussionmentioning

confidence: 99%

Active compounds of herbs ameliorate impaired cognition in APP/PS1 mouse model of Alzheimer’s disease

Shao³

et al. 2019

Aging

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“…This is linked to an increased concentration of non-bound ceruloplasmin (non-Cp) copper in plasma along with a decrease in copper bound to ceruloplasmin (Cp), which is less prone to oxidative reaction [17]. In support of this notion, several studies have reported that non-Cp copper is higher in individuals with mild cognitive impairment (MCI) and Alzheimer’s disease when compared with healthy controls [54,55,56]. Furthermore, Squitti et al [57] demonstrated that non-Cp copper was the only significant predictor of clinical conversion from MCI toward Alzheimer’s disease.…”

Section: Discussionmentioning

confidence: 99%

Greater Circulating Copper Concentrations and Copper/Zinc Ratios are Associated with Lower Psychological Distress, But Not Cognitive Performance, in a Sample of Australian Older Adults

et al. 2019

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Dyshomeostasis of copper and zinc is linked to neurodegeneration. This study investigated the relationship between circulating copper and zinc and copper/zinc ratios and cognitive function, symptoms of depression and anxiety, and neurotrophic factors in older Australian adults. In this cross-sectional study (n = 139), plasma copper, serum zinc, and neurotrophic factors (brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor, and insulin-like growth factor-1) were assessed. Cognition was assessed using the Cogstate battery and the Behavior Rating Inventory (BRI) of Executive Function (Adult version). Symptoms of anxiety and depression were assessed with the Hospital Anxiety and Depression Scale. Copper (β = −0.024; 95% CI = −0.044, −0.004; p = 0.019) and copper/zinc ratio (β = −1.99; 95% CI = −3.41, −0.57; p = 0.006) were associated with lower depressive symptoms, but not cognition. Plasma copper had a modest positive association with BDNF (β = −0.004; 95% CI = 0.000, 0.007; p = 0.021). Zinc was not associated with any of the outcomes. In conclusion, greater circulating copper concentrations and higher copper/zinc ratios were associated with lower depressive symptoms (but not cognition), with copper also positively associated with BDNF concentration, in a sample of community-dwelling older adults.

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“…Total copper and the ratio of copper to non-heme iron distinguished progressive MCI subjects from cognitively stable MCI subjects in a five-year follow-up study [37]. Other cross-sectional studies also demonstrated that noncp-Cu is higher in MCI than in healthy controls [219,231,232]. Large population studies suggest that copper imbalances occur at early stages of cognitive loss and AD development, and copper in the soil has been associated with increased mortality relating to AD (Table 1) [233].…”

Section: Clinical Evidence: Copper Dyshomeostasis In Admentioning

confidence: 92%

Copper imbalance in Alzheimer’s disease: Convergence of the chemistry and the clinic

Kepp

Squitti

2019

Coordination Chemistry Reviews

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Content 1. Introduction 2. The amyloid hypothesis and its main problems 3. Brain copper homeostasis 4. The critical Kd of CuAD 5. Clinical evidence: Copper dyshomeostasis in AD 6. Biochemical evidence: APP/Aβ and copper transport 7. Molecular mechanisms of copper toxicity in CuAD 8. Analogies to other Cu-related diseases 9. Combining the facts into a simple model of AD due to copper dyshomeostasis 10. Conclusions

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Serum Non-Ceruloplasmin Non-Albumin Copper Elevation in Mild Cognitive Impairment and Dementia due to Alzheimer’s Disease: A Case Control Study

Cited by 25 publications

References 34 publications

Active compounds of herbs ameliorate impaired cognition in APP/PS1 mouse model of Alzheimer’s disease

Active compounds of herbs ameliorate impaired cognition in APP/PS1 mouse model of Alzheimer’s disease

Greater Circulating Copper Concentrations and Copper/Zinc Ratios are Associated with Lower Psychological Distress, But Not Cognitive Performance, in a Sample of Australian Older Adults

Copper imbalance in Alzheimer’s disease: Convergence of the chemistry and the clinic

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