Probable Reasons for Neuron Copper Deficiency in the Brain of Patients with Alzheimer’s Disease: The Complex Role of Amyloid

Alzheimer’s disease is a progressive neurodegenerative disorder that eventually leads the affected patients to die. The appearance of senile plaques in the brains of Alzheimer’s patients is known as a main symptom of this disease. The plaques consist of different components, and according to numerous reports, their main components include beta-amyloid peptide and transition metals such as copper. In this disease, metal dyshomeostasis leads the number of copper ions to simultaneously increase in the plaques and decrease in neurons. Copper ions are essential for proper brain functioning, and one of the possible mechanisms of neuronal death in Alzheimer’s disease is the copper depletion of neurons. However, the reason for the copper depletion is as yet unknown. Based on the available evidence, we suggest two possible reasons: the first is copper released from neurons (along with beta-amyloid peptides), which is deposited outside the neurons, and the second is the uptake of copper ions by activated microglia.

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Emerging Proof of Protein Misfolding and Interactions in Multifactorial Alzheimer's Disease

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200601161703 ◽

2020 ◽

Vol 20 (26) ◽

pp. 2380-2390 ◽

Cited By ~ 8

Author(s):

Md. Sahab Uddin ◽

Abdullah Al Mamun ◽

Md. Ataur Rahman ◽

Tapan Behl ◽

Asma Perveen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Protein Misfolding ◽

Neurodegenerative Disorder ◽

Senile Plaques ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Misfolded Proteins ◽

Cell Organelles ◽

The Impact

Objective: Alzheimer's disease (AD) is a devastating neurodegenerative disorder, characterized by the extracellular accumulations of amyloid beta (Aβ) as senile plaques and intracellular aggregations of tau in the form of neurofibrillary tangles (NFTs) in specific brain regions. In this review, we focus on the interaction of Aβ and tau with cytosolic proteins and several cell organelles as well as associated neurotoxicity in AD. Summary: Misfolded proteins present in cells accompanied by correctly folded, intermediately folded, as well as unfolded species. Misfolded proteins can be degraded or refolded properly with the aid of chaperone proteins, which are playing a pivotal role in protein folding, trafficking as well as intermediate stabilization in healthy cells. The continuous aggregation of misfolded proteins in the absence of their proper clearance could result in amyloid disease including AD. The neuropathological changes of AD brain include the atypical cellular accumulation of misfolded proteins as well as the loss of neurons and synapses in the cerebral cortex and certain subcortical regions. The mechanism of neurodegeneration in AD that leads to severe neuronal cell death and memory dysfunctions is not completely understood until now. Conclusion: Examining the impact, as well as the consequences of protein misfolding, could help to uncover the molecular etiologies behind the complicated AD pathogenesis.

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Structural and functional aspects of membranes

10.36253/978-88-6655-445-5 ◽

2014 ◽

Author(s):

Elisa Evangelisti

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Stromal Cells ◽

Senile Plaques ◽

Cellular Membrane ◽

Cholesterol Content ◽

Amyloid Peptide ◽

Amyloid Toxicity ◽

Functional Aspects ◽

Physicochemical Features

Alzheimer’s disease (AD) is a common form of dementia characterized by the formation of extracellular senile plaques composed of aggregated amyloid peptide (Aβ). The present studies provide evidence that: cell resistance to amyloid toxicity is related to lipid raft cholesterol content. Cholesterol and GM1, affect the susceptibility of Familial Alzheimer’s Disease (FAD) broblasts to Aβ42 oligomers in opposite ways, by modulating amyloid binding to lipid rafts and its subsequent toxic effects. The degree of toxicity of the oligomeric species results from a complex interplay between the structural and physicochemical features of both the oligomers and the cellular membrane. Neuronal differentiation of human mesenchymal stromal cells increases their resistance to Aβ42 aggregate toxicity.

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Aß Monomer, Oligomer and Fibril in Alzheimer's Disease

Early Detection and Rehabilitation Technologies for Dementia ◽

10.4018/978-1-60960-559-9.ch016 ◽

2011 ◽

pp. 125-131

Author(s):

Hiroshi Mori

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Disorder ◽

Senile Plaques ◽

Amyloid Angiopathy ◽

Gamma Secretase ◽

Aged People ◽

Theoretical Predictions ◽

Prevalent Disease

Alzheimer’s disease (AD), the most prevalent disease of aged people, is a progressive neurodegenerative disorder with dementia. Amyloid-ß (also known as ß-protein and referred to here as Aß) is a well-established, seminal peptide in AD that is produced from the amyloid precursor protein (APP) by consecutive digestion with the ß secretase of BACE (beta-site amyloid cleaving enzyme) and gamma secretase of the presenilin complex. Abnormal cerebral accumulation of Abeta in the form of insoluble fibrils in senile plaques and cerebral amyloid angiopathy (CAA) is a neuropathological hallmark of AD. In contrast to insoluble fibrillary Aß, a soluble oligomeric complex, ADDL, consists of low-n oligomers of Aß, such as Aß*56. Despite their different names, it is currently proposed that oligomeric Aß is directly involved in synaptic toxicity and cognitive dysfunction in the early stages of AD. This chapter identifies a novel APP mutation (E693delta; referred to as the Osaka mutation) in a pedigree with probable AD, resulting in a variant Aß lacking glutamate at position 22. Based on theoretical predictions and in vitro studies on synthetic mutant Aß peptides, the mutated Aß peptide showed a unique and enhanced oligomerization activity without fibrillization. This was further confirmed by PiB-PET analysis on the proband patient. Collectively, the chapter concludes that the Osaka mutation is the first human evidence for the hypothesis that oligomeric Aß is involved in AD.

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Modulating Effect of Diet on Alzheimer’s Disease

Diseases ◽

10.3390/diseases7010012 ◽

2019 ◽

Vol 7 (1) ◽

pp. 12 ◽

Cited By ~ 6

Author(s):

Paloma Fernández-Sanz ◽

Daniel Ruiz-Gabarre ◽

Vega García-Escudero

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Inflammatory Response ◽

Scientific Evidence ◽

Senile Plaques ◽

Neuronal Loss ◽

Pleiotropic Effect ◽

Amyloid Peptide ◽

Dietary Recommendations

As life expectancy is growing, neurodegenerative disorders, such as Alzheimer’s disease, are increasing. This disease is characterised by the accumulation of intracellular neurofibrillary tangles formed by hyperphosphorylated tau protein, senile plaques composed of an extracellular deposit of β-amyloid peptide (Aβ), and neuronal loss. This is accompanied by deficient mitochondrial function, increased oxidative stress, altered inflammatory response, and autophagy process impairment. The present study gathers scientific evidence that demonstrates that specific nutrients exert a direct effect on both Aβ production and Tau processing and their elimination by autophagy activation. Likewise, certain nutrients can modulate the inflammatory response and the oxidative stress related to the disease. However, the extent to which these effects come with beneficial clinical outcomes remains unclear. Even so, several studies have shown the benefits of the Mediterranean diet on Alzheimer’s disease, due to its richness in many of these compounds, to which can be attributed their neuroprotective properties due to the pleiotropic effect they show on the aforementioned processes. These indications highlight the potential role of adequate dietary recommendations for clinical management of both Alzheimer’s diagnosed patients and those in risk of developing it, emphasising once again the importance of diet on health.

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O1-11-04: PGlu-beta-amyloid peptides, highly abundant in Alzheimer's disease brain, are cytotoxic in vitro , in situ and in vivo

Alzheimer s & Dementia ◽

10.1016/j.jalz.2013.04.113 ◽

2013 ◽

Vol 9 ◽

pp. P152-P152

Author(s):

Hans Demuth ◽

Rico Eichentopf ◽

Raik Rönicke ◽

Klaus G. Reymann ◽

Stephan Schilling

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Beta Amyloid ◽

Amyloid Peptides

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Paper-Based Detection Device for Alzheimer’s Disease—Detecting β-amyloid Peptides (1–42) in Human Plasma

Diagnostics ◽

10.3390/diagnostics10050272 ◽

2020 ◽

Vol 10 (5) ◽

pp. 272

Author(s):

Wei-Hsuan Sung ◽

Jung-Tung Hung ◽

Yu-Jen Lu ◽

Chao-Min Cheng

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Operating Time ◽

Amyloid Peptide ◽

Buffer System ◽

Amyloid Peptides ◽

Β Amyloid ◽

Β Amyloid Peptide ◽

Short Operating Time ◽

Tremendous Impact

The diagnosis of Alzheimer’s disease (AD) is frequently missed or delayed in clinical practice. To remedy this situation, we developed a screening, paper-based (P-ELISA) platform to detect β-amyloid peptide 1–42 (Aβ42) and provide rapid results using a small volume, easily accessible plasma sample instead of cerebrospinal fluid. The protocol outlined herein only requires 3 μL of sample per well and a short operating time (i.e., only 90 min). The detection limit of Aβ42 is 63.04 pg/mL in a buffer system. This P-ELISA-based approach can be used for early, preclinical stage AD screening, including screening for amnestic mild cognitive impairment (MCI) due to AD. It may also be used for treatment and stage monitoring purposes. The implementation of this approach may provide tremendous impact for an afflicted population and may well prompt additional and expanded efforts in both academic and commercial communities.

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