Non-Ceruloplasmin Copper Distinguishes A Distinct Subtype of Alzheimer's Disease: A Study of EEG-Derived Brain Activity

Tecchio, Franca; Vecchio, Fabrizio; Ventriglia, Mariacarla; Porcaro, Camillo; Miraglia, Francesca; Siotto, Mariacristina; Rossini, Paolo Maria; Rongioletti, Mauro; Squitti, Rosanna

doi:10.2174/1567205013666160603001131

Cited by 25 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These recent researches have contributed considerably to the explanation of the previous controversy. In blood, a higher level of free plasma Cu, which has been identified in 50–60% of Alzheimer’s patients, can explain the higher level of serum Cu in AD [ 145 , 174 , 233 , 236 ]. Another earlier research also observed an increased concentration of serum copper ions in a special kind of AD (Alzheimer’s disease epsilon four apolipoprotein E allele carriers) [ 237 ].…”

Section: Contradictory Results About Copper Level In Admentioning

confidence: 99%

Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches

Ejaz

Wang

Lang

2020

IJMS

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is an irreversible, age-related progressive neurological disorder, and the most common type of dementia in aged people. Neuropathological lesions of AD are neurofibrillary tangles (NFTs), and senile plaques comprise the accumulated amyloid-beta (Aβ), loaded with metal ions including Cu, Fe, or Zn. Some reports have identified metal dyshomeostasis as a neurotoxic factor of AD, among which Cu ions seem to be a central cationic metal in the formation of plaque and soluble oligomers, and have an essential role in the AD pathology. Cu-Aβ complex catalyzes the generation of reactive oxygen species (ROS) and results in oxidative damage. Several studies have indicated that oxidative stress plays a crucial role in the pathogenesis of AD. The connection of copper levels in AD is still ambiguous, as some researches indicate a Cu deficiency, while others show its higher content in AD, and therefore there is a need to increase and decrease its levels in animal models, respectively, to study which one is the cause. For more than twenty years, many in vitro studies have been devoted to identifying metals’ roles in Aβ accumulation, oxidative damage, and neurotoxicity. Towards the end, a short review of the modern therapeutic approach in chelation therapy, with the main focus on Cu ions, is discussed. Despite the lack of strong proofs of clinical advantage so far, the conjecture that using a therapeutic metal chelator is an effective strategy for AD remains popular. However, some recent reports of genetic-regulating copper transporters in AD models have shed light on treating this refractory disease. This review aims to succinctly present a better understanding of Cu ions’ current status in several AD features, and some conflicting reports are present herein.

show abstract

Section: Contradictory Results About Copper Level In Admentioning

confidence: 99%

Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches

Ejaz

Wang

Lang

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Recent studies have contributed to unraveling further the initial controversy, demonstrating that the increased concentration of serum copper in AD can be explained by the increased concentrations of the plasma fraction of the “free” copper pool in the blood, which is detected in only 50–60% of AD patients ( Squitti et al, 2016 ; Szabo et al, 2016 ; Tecchio et al, 2016 ; Talwar et al, 2017 ). An older study also indicated that serum copper concentration rises in a special type of AD ( González et al, 1999 ).…”

Section: Copper Ion Toxicity In Admentioning

confidence: 99%

Role of Copper in the Onset of Alzheimer’s Disease Compared to Other Metals

Bagheri

Squitti

Haertlé

et al. 2018

Front. Aging Neurosci.

Self Cite

174

121

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by amyloid plaques in patients’ brain tissue. The plaques are mainly made of β-amyloid peptides and trace elements including Zn2+, Cu2+, and Fe2+. Some studies have shown that AD can be considered a type of metal dyshomeostasis. Among metal ions involved in plaques, numerous studies have focused on copper ions, which seem to be one of the main cationic elements in plaque formation. The involvement of copper in AD is controversial, as some studies show a copper deficiency in AD, and consequently a need to enhance copper levels, while other data point to copper overload and therefore a need to reduce copper levels. In this paper, the role of copper ions in AD and some contradictory reports are reviewed and discussed.

show abstract

“…The axonal terminals and secretory granules, as well as the synaptic cleft, is highly enriched with Cu (up to 100 mol/L) upon glutamatergic neurotransmission and is a primary and early target of AD-related pathogenic mechanisms[125]. These processes have been linked to non-Cp Cu excess associated neurophysiological abnormalities[2,126].Systemic commonalities to other diseasesAs mentioned above, most sporadic cases of AD are probably driven by a combination of neuropathological, vascular, metabolic, and neuroinflammatory pathogenic pathways, which may have an age-aggravated systemic feature in common: energyU n c o r r e c t e d A u t h o r P r o o f deficits. Neurons are among the most energydemanding cells in the body.…”

mentioning

confidence: 99%

Copper Imbalance in Alzheimer’s Disease and Its Link with the Amyloid Hypothesis: Towards a Combined Clinical, Chemical, and Genetic Etiology

Squitti

Faller

Hureau

et al. 2021

JAD

Self Cite

View full text Add to dashboard Cite

The cause of Alzheimer’s disease (AD) is incompletely defined. To date, no mono-causal treatment has so far reached its primary clinical endpoints, probably due to the complexity and diverse neuropathology contributing to the neurodegenerative process. In the present paper, we describe the plausible etiological role of copper (Cu) imbalance in the disease. Cu imbalance is strongly associated with neurodegeneration in dementia, but a complete biochemical etiology consistent with the clinical, chemical, and genetic data is required to support a causative association, rather than just correlation with disease. We hypothesize that a Cu imbalance in the aging human brain evolves as a gradual shift from bound metal ion pools, associated with both loss of energy production and antioxidant function, to pools of loosely bound metal ions, involved in gain-of-function oxidative stress, a shift that may be aggravated by chemical aging. We explain how this may cause mitochondrial deficits, energy depletion of high-energy demanding neurons, and aggravated protein misfolding/oligomerization to produce different clinical consequences shaped by the severity of risk factors, additional comorbidities, and combinations with other types of pathology. Cu imbalance should be viewed and integrated with concomitant genetic risk factors, aging, metabolic abnormalities, energetic deficits, neuroinflammation, and the relation to tau, prion proteins, α-synuclein, TAR DNA binding protein-43 (TDP-43) as well as systemic comorbidity. Specifically, the Amyloid Hypothesis is strongly intertwined with Cu imbalance because amyloid-β protein precursor (AβPP)/Aβ are probable Cu/Zn binding proteins with a potential role as natural Cu/Zn buffering proteins (loss of function), and via the plausible pathogenic role of Cu-Aβ.

show abstract

Non-Ceruloplasmin Copper Distinguishes A Distinct Subtype of Alzheimer's Disease: A Study of EEG-Derived Brain Activity

Abstract: This neurophysiological heterogeneity in EEG-derived brain cortical rhythms between the two AD groups sustains a copper AD metabolic subtype; Non-Cp-Cu is a marker of this copper AD.

Cited by 25 publications

References 0 publications

Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches

Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches

Role of Copper in the Onset of Alzheimer’s Disease Compared to Other Metals

Copper Imbalance in Alzheimer’s Disease and Its Link with the Amyloid Hypothesis: Towards a Combined Clinical, Chemical, and Genetic Etiology

Contact Info

Product

Resources

About