Abnormal calcium levels in mitochondria may cause neuronal cell death in Alzheimer's disease

For the first time, using a mouse model of Alzheimer's disease, scientists have documented a link between raised levels of calcium in mitochondria and neuronal death in the living brain.

This relationship was previously documented in cell culture, but seeing this phenomenon in living mice makes it more likely that this occurs in people also and could point to a new target for Alzheimer's disease.

We were able to show mitochondrial calcium dysregulation in the neurons of living mice with Alzheimer's-like symptoms using cutting edge live imaging techniques."

Maria Calvo-Rodriguez, PhD, Study Lead Author, Department of Neurology at Massachusetts General Hospital.

One of the defining hallmarks of Alzheimer's disease is the deposition of amyloid beta plaques and loss of neurons. The accumulation of amyloid beta has long been thought to be a trigger of the disease, but the exact means by which neurons die in Alzheimer's remain a mystery, and the amyloid beta theory has become controversial because so many drug candidates targeting amyloid beta have failed in clinical trials.

One of the effects of amyloid beta plaques is that they cause high calcium ion (Ca2+) levels in the brain cells. There is also evidence that, at least in cell culture, exposure to amyloid beta can raise Ca2+ levels within mitochondria and lead to neuronal death.

Mitochondria influence Ca2+ signaling inside neurons through the "mitochondrial calcium uniporter" that takes up Ca2+ into mitochondria. The investigation of this mechanism in living mice has been hampered by the lack of technologies sensitive enough to directly assess Ca2+ levels in mitochondria in the living brain.

To explore the relationship between Ca2+, mitochondria and neuronal death, Calvo-Rodriguez and her colleagues combined multiphoton-microscopy with a ratiometric Ca2+ indicator targeted to mitochondria to asses Ca2+ levels. They applied these technologies to examine the neurons of a transgenic mouse model of Alzheimer's disease that develops amyloid plaques similar to those from human patients.

Their studies demonstrate that increased mitochondrial Ca2+ levels are associated with plaque deposition and neuronal death in this model, indicating that abnormal Ca²⁺ levels in mitochondria could play a role in neuronal cell death in Alzheimer's disease.

Additionally, they observed that when soluble Aβ is applied to the healthy mouse brain Ca2+ concentration in mitochondria increases. That process can be prevented by blockage of the mitochondrial calcium uniporter with a drug. Soluble amyloid beta is a type of amyloid beta similar to that in the human Alzheimer's brain.

"High calcium levels in the mitochondria cause oxidative stress, and the death of neurons via apoptosis," says Calvo-Rodriguez. "We propose that by blocking the neuronal mitochondrial calcium uniporter we can prevent cell death and impact disease progression." Their work suggests targeting calcium entry to the mitochondria could be a promising new therapeutic approach in Alzheimer's disease.

This is only for your information, kindly take the advice of your doctor for medicines, exercises and so on.     

https://gscrochetdesigns.blogspot.com. one can see my crochet creations  
https://gseasyrecipes.blogspot.com. feel free to view for easy, simple and healthy recipes    
https://kneereplacement-stickclub.blogspot.com. for info on knee replacement

Alzheimer's Zombie-like Cells Cure

A type of cellular stress that is linked to both cancer and aging has now also been found to be connected to Alzheimer's disease. Some researchers recently reported this discovery in the scientific journal, and it is being hailed by leading scientists as a potentially massive step forward.

The researchers discovered that this stress, known as cellular senescence, is linked to dangerous tau protein tangles that are a hallmark of 20 different brain conditions, including traumatic brain injury and dementia. The scientists identified senescent cells in postmortem brain tissue from sufferers of Alzheimer's. They then also discovered these cells in postmortem tissue from sufferers of progressive supranuclear palsy, another kind of brain disease.
While cellular senescence does not outright kill the cell, it may cause it to become zombie-like, altering its functions and killing surrounding cells. According to a study, the senior author says, "when cells enter this stage, they change their genetic programming and become pro-inflammatory and toxic."
The team used a number of different types of medication to clear senescent cells out from the brains of 4 types of middle-aged Alzheimer's mice. The most effective 2 were quercetin, a natural flavonoid compound, and dasatinib, a chemotherapy medication.

Very promising results were seen after 3 months of treatment. "The mice were 20 months old and had advanced brain disease when we started the therapy," according to the Dr. "After clearing the senescent cells, we saw improvements in brain structure and function. This was observed in brain MRI studies (magnetic resonance imaging) and postmortem histology studies of cell structure. The treatment seems to have stopped the disease in its tracks."
One of the study's primary authors said that "the fact we were able to treat very old mice and see improvement gives us hope that this treatment might work in human patients even after they exhibit symptoms of a brain disease." This is because when testing cures for Alzheimer's, therapy usually only works if mice are treated prior to the disease's onset.
In Alzheimer's disease, the sufferer's brain tissue accumulates tangles of tau protein, in addition to another protein deposit known as amyloid beta plaque. The researchers discovered that it is tau accumulation that is responsible for cell senescence. The team compared Alzheimer's mice that had only amyloid beta plaques with mice that had only tau tangles. They found that senescence only took place in those mice that had tau tangles.

Amazingly, the combination of drugs administered did not merely decrease the occurrence of cell senescence, but also the tau tangles themselves. "When we looked at their brains three months later, we found that the brains had deteriorated less than mice that received placebo control treatment," Dr. said. "We don't think brain cells actually grew back, but there was less loss of neurons, less brain ventricle enlargement, improved cerebral blood flow and a decrease in the tau tangles. These drugs were able to clear the tau pathology."
According to the Dr., "this is the first of what we anticipate will be many studies to better understand this process," and that since "these drugs are approved for other uses in humans, we think a logical next step would be to start pilot studies in people."
Some great news is that these drugs are designed to only target and kill senescent cells and nothing else. What's more, due to their short half-life, they quickly disappear from the body and are not known to cause any negative side effects. Of course, human dosage and frequency will still need to be determined through clinical trials.

Dasatinib is an oral medication with which the mice were treated only once a fortnight. "So in the three months of treatment, they only received the drug six times," Dr. Orr claimed. "The drug goes in, does its job and is cleared. Senescent cells come back with time, but we expect that it would be possible to take the drug again and be cleared out again. That's a huge benefit - it wouldn't be a drug that people would have to take every day."
The next step for the researchers will be to work out whether cell senescence is a part of traumatic brain injury, too. According to Dr. Orr, TBI is a brain injury which also causes an accumulation of tau proteins, and is a significant cause of disability for military personnel and many others.

THIS IS ONLY FOR INFORMATION, ALWAYS CONSULT YOU PHYSICIAN BEFORE HAVING ANY PARTICULAR FOOD/ MEDICATION/EXERCISE/OTHER REMEDIES.                                                                                                                                                                                                        PS- THOSE INTERESTED IN RECIPES ARE FREE TO  VIEW MY BLOG-                                                                                           https://gseasyrecipes.blogspot.com/  

FOR INFO ABOUT KNEE REPLACEMENT, YOU CAN VIEW MY BLOG-                                                                                        https:// kneereplacement-stickclub.blogspot.com/                              
FOR CROCHET DESIGNS                                                                                                                                                                                                                                 https://gscrochetdesigns.blogspot.com

New blood test detects early signs of Alzheimer's disease

Raising hopes for an effective intervention in diagnosing the risk of early onset of disease, German scientists have developed a new blood test that can detect Alzheimer's long before the first symptoms appear in patients.

Alzheimer's disease is thought to begin long before patients show typical symptoms like memory loss. 

The team, noted that one of the hallmarks of Alzheimer's disease is the accumulation of amyloid-beta plaques in the patient's brain. 

The findings,  showed that the blood test uses a technology called immuno-infrared sensor to measure distribution of pathological and healthy structures of amyloid-beta in the blood.

The pathological amyloid-beta structure is rich in a sticky, sheet-like folding pattern that makes it prone to aggregation, while the healthy structure is not.

The two structures absorb infrared light at a different frequency, allowing the blood test to determine the ratio of healthy to pathological amyloid-beta in the sample. 

The pathological form is a mis-folded version of this molecule and known to initiate the formation of toxic amyloid-beta molecules that starts accumulating in the brain 15 to 20 years before disease onset. 

They found that the test reliably detected amyloid-beta alterations in the blood of participants with mild cognitive impairment that also showed abnormal amyloid deposits in brain scans.

In order to detect blood changes well ahead of disease onset, the researchers compared blood samples of 65 participants that were later in the follow-up studies diagnosed with Alzheimer's disease with 809 controls. 

The assay was able to detect signs of the disease on average eight years before diagnosis in individuals without clinical symptoms with an overall diagnostic accuracy of 86 per cent. 

The blood test would thus offer an opportunity to identify those at risk and may thereby open the door to new avenues in drug discovery, the researchers said.

THIS IS ONLY FOR INFORMATION, ALWAYS CONSULT YOU PHYSICIAN BEFORE HAVING ANY PARTICULAR FOOD/ MEDICATION/EXERCISE/OTHER REMEDIES.                                                                                                                                                                                                      PS- THOSE INTERESTED IN RECIPES ARE FREE TO VIEW MY BLOG-                                                                                           https://gseasyrecipes.blogspot.com/   
FOR INFO ABOUT KNEE REPLACEMENT, YOU CAN VIEW MY BLOG-                                                           https:// kneereplacement-stickclub.blogspot.com/                              
FOR CROCHET DESIGNS                                                                                                                                                                                                                                         https://my crochet creations.blogspot.com/