Characterization of plasma metal profiles in Alzheimer’s disease using multivariate statistical analysis

Chen, Guan; Dang, Rui; Liu, Liyan; Chen, Xiaobei; Wang, Xiaoyu; Zhu, Jingli; Li, Donggang; Li, Junwei; Wang, Decai

doi:10.1371/journal.pone.0178271

Cited by 22 publications

(10 citation statements)

References 37 publications

(36 reference statements)

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“…In this study, plasma zinc levels in AD were signi cantly lower than that of controls; this corroborates the ndings in different studies (28,29). The brain has been reported to be second only to the beta cells of the pancreas to contain the highest concentration of zinc (30), where it performs diverse roles in key processes such as enzymatic activity, neurotransmitter release and modulation of gated ion channels for synaptic transmission (31).…”

Section: Discussionsupporting

confidence: 91%

Oxidative Stress, Trace and Toxic Metal Levels In Alzheimer’S Disease In Sub-Sahara Africa

Omotosho

Ngwube

Abdumalik

2020

Preprint

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BackgroundAlzheimer’s disease (AD), an age-related neurodegenerative disease characterized by loss of memory has been attributed to oxidative stress induced by accumulation of Amyloid (Aβ) protein in the brain; environmental and genetic alterations have been implicated as the pathogenesis of the disease. This work investigated levels of selected trace (Iron, Zinc and Copper) and toxic (Cadmium and Lead) metals in AD patients.MethodIn this case-control study, a total of 38 participants (aged ≥ 60 years) consisting of 18 clinically diagnosed AD subjects and 20 apparently healthy age-matched adults were recruited from the University College Hospital Ibadan Geriatric Centre. Semi-structured questionnaire was used to obtain demographic information, clinical history, lifestyle and dietary patterns from participants. Blood levels of iron, copper, zinc, lead and cadmium were analyzed using Atomic Absorption Spectrophotometry (AAS); levels of malondialdehyde (MDA), total antioxidant capacity (TAC), hydrogen peroxide (H2O2), and total plasma peroxide (TPP) were determined spectrophotometrically, while oxidative stress index (OSI) and copper to zinc ratio (Cu:Zn) were calculated.ResultsMean plasma level of zinc was significantly lower in cases (86.04 ± 11.07 µg/dl) compared to controls (108.80 ± 12.47 µg/dl), while blood lead (13.85 ± 2.96 µg/dl, 8.32 ± 2.10 µg/dl) and cadmium (1.34 ± 0.71 µg/L, 0.71 ± 0.14 µg/L) levels were significantly higher in cases than in controls respectively. Although Fe and Cu levels were similar in cases and controls, Cu:Zn ratio was significantly elevated in cases compared to controls (p = 0.000). Though other OS markers were not significantly different in both groups, TPP was significantly higher in cases (64.96 ± 7.20 µmol/H2O2 vs. 55.41 ± 2.38 µmol/H2O2) while MDA correlated inversely with TAC in cases (r= − 0.477, p = 0.045).DiscussionThe low plasma Zn coupled with high blood Pb and Cd levels may precipitate the elevated TPP and Cu:Zn ratio in cases. The reduced metallothionine defense of the system as indicated by the elevated Cu:Zn ratio in cases may also exacerbate this problem.ConclusionThe damaging effect of increasing toxic metal levels may be accentuating development of oxidative stress facilitating the progression of AD.

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Section: Discussionsupporting

confidence: 91%

Oxidative Stress, Trace and Toxic Metal Levels In Alzheimer’S Disease In Sub-Sahara Africa

Omotosho

Ngwube

Abdumalik

2020

Preprint

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“…According to the very recent meta-analysis, which includes a total of 35 pieces of research: eighteen report an increase, fourteen show no change, and one reports a decrease in Cu level in the serum-plasma of this disorder [ 232 ]. Subsequently, three more studies have been published, stating increased Cu 2+ ions level in Alzheimer’s compared to that in the healthy controls [ 233 , 234 , 235 ].…”

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

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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.

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“…More specifically, the large stand most recent meta-analysis (total pool of subjects analyzed: 2128 AD vs. 2889 healthy controls) includes a total of 35 studies: 18 report an increase, 14 no difference, and one a decrease in values of copper in the serum–plasma in AD compared to healthy controls ( Li et al, 2017 ). Three additional studies appeared after the publication of this consensus result ( Guan et al, 2017 ; Pu et al, 2017 ; Talwar et al, 2017 ), reporting increased concentrations of Cu 2+ in AD patients vs. controls.…”

Section: Copper Ion Toxicity In Admentioning

confidence: 93%

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

Bagheri

Squitti

Haertlé

et al. 2018

Front. Aging Neurosci.

172

121

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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.

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Characterization of plasma metal profiles in Alzheimer’s disease using multivariate statistical analysis

Cited by 22 publications

References 37 publications

Oxidative Stress, Trace and Toxic Metal Levels In Alzheimer’S Disease In Sub-Sahara Africa

Oxidative Stress, Trace and Toxic Metal Levels In Alzheimer’S Disease In Sub-Sahara Africa

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

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