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Scientists identify brain metals that drive the progression of Alzheimer’s disease

Alzheimer’s disease is a progressive, chronic disease that attacks the brain cells and neurons; dementia is the first clinical symptom of this disease, which normally afflicts people in the old age. Alzheimer’s is a serious illness that impairs the cognitive skills of the patient to such an extent that they need to be under the supervision of assisted care. Such an ailment could be understood better if scientists identify the metals of the brain, which are involved in instigating the neurodegenerative condition. Such a research study was recently completed by an international group of researchers through a collaborative approach. The research team was headed by Dr. Joanna Collingwood, who works at the School of Engineering, University of Warwick.

This research team reported that iron species in the brain could be characterized easily as they play a pivotal role in the formation of plaques caused by amyloid proteins; these proteins are extensively found in the human brain. Clustering of these proteins may reach an abnormal level, leading to the formation of plaques. The toxicity of these plaques is severe, causing apoptosis (programmed cell death) of tissues. With the progressive of tissues in the brain, the person’s cognitive skills decline consistently; memory loss is followed by deterioration in mental condition and the patient ultimately develops Alzheimer’s disease.

In patients with Alzheimer’s disease, the plaques formed by amyloid proteins are unique and can be characterized easily. The iron species are otherwise in their normal state in a healthy human brain. When a person develops Alzheimer’s disease, these iron species undergo extensive chemical reduction. This leads to the formation of a chemically reduced species named magnetite; the proliferation of magnetite occurs in the amyloid protein plaques. The team of researchers believes that magnetite is the result of the chemical interaction between iron species and amyloid proteins in the human brain afflicted with Alzheimer’s illness.

In advanced countries, like the USA and UK, there have been several advancements in diagnostic technologies used for the analysis of human brain. One such advancement is the introduction of Diamond Light Source 108 beamline instrument in Oxfordshire, UK. This sophisticated instrument is capable of performing advanced measurements of the human brain using synchrotron X-rays. The team of researchers at the University of Warwick used this instrument to gather evidences for their work. They were successful in proving that detailed chemical reduction of metallic species only took place in the human brain of individuals afflicted with Alzheimer’s disease. They further reported about the different forms of calcium species that were present in the form of minerals in the plaques formed by amyloid protein.

What exactly is the significance of this discovery? Well, we have now understood that metals in the human brain undergo a lot of chemical reduction and transformation when a person is afflicted with Alzheimer’s disease. This would help us in further discovering the root cause of the disease. By correlating the concentration of these reduced metal species with the progression of the disease, scientists can develop more innovative therapies that can exactly eradicate the root cause of the disease.

Dr. Joanna Collingwood, who is the supervisor leading this team of international researchers, works as an Associate Professor at the School Engineering, University of Warwick. She is an expert in following analytical techniques of measurement: trace metal analysis and high resolution imaging. She has used these skills to understand and elucidate the pathophysiology of neurodegenerative diseases, including Alzheimer’s disease.

According to Dr. Collingwood, we need to know the guiding principle of this research study: Iron is an essential element in the human brain, so it is but natural that we comprehensively understand how the fluctuations in iron levels could be associated with the development of Alzheimer’s disease. It is important to note that we are only concerned about iron levels in the human brain at this stage of research. We used sophisticated X-ray techniques in this study to understand how iron undergoes a step-wise change in its neurochemistry while interacting with amyloid proteins, which cluster together excessively to form plaques. It is interesting to note how amyloid protein formation instigates a massive chemical change in the composition of iron species, which are found extensively in the human brain. Previous studies have attempted to treat Alzheimer’s disease with iron-based drugs. Our findings would only alleviate further research studies in this direction, leading to the development of novel drugs based on iron.

The research study was conducted by an international collaboration between researchers working at the following institutions: University of Warwick and Keele University. It also included researchers working at the following institutions: University of Texas in San Antonio and University of Florida. To form an insight into this path-breaking discovery, the team of researchers first successfully extracted the cores formed by amyloid protein plaques; these were obtained from the human brain of two deceased patients who had succumbed to Alzheimer’s disease.

For the purpose of scanning the cores formed by amyloid plaques, researchers used the following sophisticated analytical instrument: an advanced X-ray microscope was obtained from the Advanced Light Source in Berkeley, USA. The Diamond Light Source synchrotron (beamline 108) was also used in this study; this instrument was obtained from Oxfordshire and its main purpose was to determine the chemical properties of the altered minerals found in the brain of these deceased patients. With the help of these sophisticated instruments, the researchers also analyzed whether all the iron species had undergone a change in its magnetic state when they interacted with the amyloid proteins in the plaques. Researchers tried to find out if there were any unchanged iron species in the plaques. Magnetite, the leading magnetic form of iron oxide, was found extensively in these plaques. Other minerals of altered iron species were also found in these plaques.

Significance: The UK is a small country with the best healthcare system in the world. Sadly, it still cannot cure about 850,000 patients diagnosed with dementia, the first clinical symptom of Alzheimer’s disease. The number of patients with Alzheimer’s disease is expected to be skyrocketing at 1 million and 2 million by 2025 and 2050, respectively. Presently, medical science has no cure for this disease and other conditions that cause dementia. If the development of dementia in Alzheimer’s patients is delayed by at least five years, the number of deaths caused by this condition could be halved easily. This implies that approximately 30,000 patients could be prevented from untimely death; their lives can be saved with this path-breaking discovery.

Conclusion: Researchers believe that the development and progression of Alzheimer’s disease is associated with the chemical reduction of iron species in the human brain. The resultant iron species have an altered magnetic state; the most prominent among them being magnetite. All these altered iron species are highly toxic in nature, creating conducive conditions for Alzheimer’s disease.

 

 

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Can Alzheimer’s be treated with aspirin?

Plaques developed in the brain can be eliminated with a low-dose aspirin, which is an effective drug that suppresses the progression of Alzheimer’s disease. The drug aspirin is very effective in protecting the memory of patients. These are the latest findings reported by neurologists at the Rush University Medical Center. The results of this study were published in the Journal of Neuroscience.

Our study is path-breaking and novel in the sense that aspirin is one of the most commonly used medication for various illnesses. More than 1 out of 10 Americans was diagnosed with Alzheimer’s disease, which is a progressive form of dementia. Very few drugs have been approved by the FDA for the treatment of Alzheimer’s-related complications, such as dementia. Presently, only temporary relief is provided by these medications.

Researchers still do not know the exact cause of Alzheimer’s disease; however, researchers know the cause of dementia and memory loss, which is associated with the faulty disposal of amyloid beta. Amyloid beta is the most toxic protein to have been developed in the human brain. Researchers believe that the most important strategy for eliminating the progression of Alzheimer’s illness would be the activation of cellular machinery. Waste can be removed from the human brain with this machinery.

Amyloid plaques are clumps formed by the toxic protein amyloid beta. The connection between nerve cells would be harmed by amyloid plaques. Such a development is one of the major signs of Alzheimer’s illness. There seems to be a link between the reduced risk of developing Alzheimer’s disease and the consumption of aspirin. The most important component of animal cells, the lysosomes, is very useful in clearing cellular debris. In mice, lysosomes could be stimulated with aspirin. Aspirin is the component that decreases amyloid plaque.

The incidence, progression, and development of Alzheimer’s disease could be stopped by elucidating the development of amyloid plaques. To regulate the removal of waste products from the human body, a protein named TFEB. Aspirin was administered orally to mice, which were genetically modified to develop the pathology of Alzheimer’s disease.

To determine the parts of brain most affected by Alzheimer’s disease, we determined the amount of amyloid plaque in these subjects. In mice, the functions of aspirin medications are as follows: i) to augment the expression of TFEB, ii) stimulate the expression of lysosomes, and iii) decrease the pathology of amyloid plaque.

Aspirin is the most widely used medication for pain relief; moreover, it is also used extensively for the treatment of cardiovascular diseases. The findings of these research studies must be validated further. Aspirin could be soon considered as a therapeutic drug for the treatment of Alzheimer’s illness and other diseases related to dementia.

 

 

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In Mice with Alzheimer’s, memory loss is reversed with diabetic drug

According to a recently published paper in Brain Research, a diabetic drug could be used to reverse memory loss in mice with Alzheimer’s disease. This study was conducted at Lancaster University in the UK. Professor Christian Holscher was the lead researcher of this study. This is a promising line of treatment for Alzheimer’s disease, a common neurodegenerative disorder. The drug was conventionally used to treat patients with type 2 diabetes.

Memory loss and dementia are the most common signs of Alzheimer’s disease. According to Alzheimer’s Society, more than two million people would suffer from Alzheimer’s disease by 2051. This research study was partially funded by Alzheimer’s Society. It is alarming rate of increase and there has been no new treatment for Alzheimer’s disease in recent times.

Since the past 15 years, physicians have been prescribing the same medications for patients with Alzheimer’s disease. According to Dr Doug Brown at the Alzheimer’s Society, new drugs must be urgently developed to tackle the growing number of patients with Alzheimer’s disease. Patients with Alzheimer’s disease cannot lead normal lives as dementia progresses quickly, limiting their cognitive skills and memory.

Diabetic drug liraglutide was tested on mice with Alzheimer’s disease; however, its efficacy must be further tested on human patients with Alzheimer’s disease. Randomized clinical trial need to be carried out with this objective. “Triple agonist drugs” have also shown promising results on mice with Alzheimer’s disease. Nevertheless, much needs to be done in the area of research and development.

Liraglutide is a “triple receptor drug” that has been tested for the first time. Researchers found that this drug could offer protection against degeneration of brain cells. Growth factors GLP-1, GIP, and Glucagon are combined in the formulation of the diabetic drug liraglutide. Previous studies have reported that growth signaling factors get impaired in the brain of patients with Alzheimer’s disease.

In this research study, scientists used transgenic mice APP/PSI. In these mice, they observed the expression of mutated genes, which cause Alzheimer’s disease. The same genes also undergo mutation in humans with Alzheimer’s disease. This form of Alzheimer’s is inherited through genetic mutation.

Researchers found that even in the advanced stage of neurodegeneration, memory loss could be significantly reversed in transgenic mice. By administering liraglutide drug to these aged mice, they could not improve memory but also cognitive ability. By performing maze test, they found that growth factors were enhanced in the brain of aged transgenic mice.

These growth factors in the brain would ensure normally functioning of nerve cells, preventing them from undergoing degeneration. Moreover, the drug decreased the formation of amyloid plaques in the brain of patients with Alzheimer’s disease. Furthermore, oxidative stress and chronic inflammation were reduced with the administration of this drug. Finally, the rate of nerve cell loss decreased following the action of this drug.

According to Professor Holscher, clinical trials have been successfully conducted with an older version of this drug. The promising results suggested that this drug was suitable for treating patients with Alzheimer’s disease. Although this drug was originally developed to manage type 2 diabetes, many studies have reported about its neuro-protective effects.

Our study is unique in the fact that a novel triple drug shows promising results when used as a line of treatment for Alzheimer’s disease. However, further clinical trials must be conducted in a dose-dependent manner on humans, and its efficacy must be compared with existing drugs to know whether if the novel drug is superior to existing ones.

The risk of Alzheimer’s disease is high in patients with type 2 diabetes. Quite often, Alzheimer’s disease develops with the progression of type 2 diabetes. Owing to impaired insulin levels, cerebral degeneration occurs in patients with type 2 diabetes. This leads to the development of Alzheimer’s disease.

In the brain of patients with Alzheimer’s disease, scientists have found that there is no sensitivity to insulin. They believe that neurodegenerative disorders occur due to insulin desensistization in the brain. This is because insulin exhibits neuroprotective effects as it is a growth factor in human brain.