Scientists identify vital early warning of Alzheimer’s that could lead to improved treatment

Scientists made a breakthrough in identifying molecular mechanism by which Alzheimer’s destroys the ability for brain cells to “talk” to each other. The discovery could enable doctors to predict the onset of the disease years in advance, allowing crucial early treatment.

The lead researcher, Dr. Vladimir Sytnyk, from the University of New South Wales (UNSW) School of Biotechnology and Biomolecular Sciences, explains that loss of synapses - which connect brain neurons - is one of the first changes associated with Alzheimer's disease.

Loss of synapses is one of the early signs of the disease. Synapses connect neurons in our brain. Synapses are needed for all brain functions, especially forming memories and learning.

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Dr. Sytnyk says that synapses loss occurs in the very early stages of the degenerative disease, long before the nerve cells die, when only mild cognitive impairment is observed.

Alzheimer’s is a fast progressing neurodegenerative disease that starts out slow, but deteriorates over time. Short-term memory loss is the most common early symptom. Alzheimer’s is the most common cause of dementia, accounting for about 60-70% of all dementia cases.

German psychiatrist and pathologist Dr. Alois Alzheimer first discovered the disease in 1906. Dr. Alzheimer’s saw alterations in the post-mortem brain tissue of a woman who died of an unusual mental illness. Upon performing a post-mortem brain examination he found abnormal clumps what we now know as amyloid plaques and neurofibrillary tangles - now called tau tangles.

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Considered as the hallmarks of Alzheimer’s disease, these plaques and tangles are believed to cause the death of brain cells, which leads to the disease.

Age is one of the risk factors of Alzheimer’s. People over the age of 70 are at a higher risk of developing Alzheimer’s. Approximately 80 percent of people over the age of 85 are affected by this dreaded disease.

Short-term memory loss is the most common early symptom (Image credit: Creative commons)

Alzheimer’s has been recently ranked as the third leading cause of death in the United States. An estimated 5.3 million Americans of all ages have Alzheimer’s.

In UK, around 800,000 people are affected by the disease.

Dr. Sytnyk and his team wanted to further examine brain alterations related to Alzheimer’s. They studied a brain protein known as neural cell adhesion molecule 2 (NCAM2) – part of a group of molecules that connect synapse membranes, maintaining the synaptic connections between neurons.

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Researchers used brain tissue of dead people with or without the disease. They found that people with Alzheimer’s had low levels of synaptic NCAM2 in their hippocampus.

In the brain of Alzheimer’s patients, most of the damage occurs in the hippocampus of the brain, the area which is essential in forming memories.

Moreover, through mice studies, they discovered that NCAM2 was battered by beta-amyloid. As discussed earlier, bety-amyloid is the main constituent of the plaques that accumulate in the brains of Alzheimer’s patients.

The findings shows that the loss of synapses is related to the loss of NCAM2, caused by toxic effects of beta-amyloid, according to Dr. Sytnyk. He hints that it may open up a new avenue to study treatments that can stop the destruction of NCAM2.

The research team was made up of researchers from Neuroscience Research Australia (NeuRA) and the UNSW School of Medical Sciences’ Dementia Research Unit.

They publish their work the journal Nature Communications.

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Scientists discover possible solution for Alzheimer’s immunotherapy side effects

A team of researchers from the University of Southampton in England have discovered a potential solution for the side effects caused by immunotherapy treatment for Alzheimer’s.

Alzheimer’s disease is a chronic neurodegenerative disease. The disease starts out slow but progresses with age. Death of nerve cells in the brain causes Alzheimer’s. Symptoms include memory loss, impaired cognitive skills, difficulty speaking and decision-making.

Scientists believe plaques formed by beta-amyloid (pieces of protein) and neurofibrillary tangles in the brain causes the death of brain cells. In the patients with Alzheimer’s, the total size of the brain shrinks, while the tissue have constantly lesser nerve cells and connections.

The older you get, the higher is your risk of getting Alzheimer’s. People over the age of 70 are at a higher risk of developing Alzheimer’s. Around 80% people over the age of 85 are affected by this dreaded disease.

An estimated 46.8 million people globally have dementia and Alzheimer’s is the most common form of dementia.

Around 800,000 people are affected by Alzheimer’s in the UK.

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Immunotherapy is a hopeful approach for the treatment of Alzheimer’s. The procedure uses antibodies to prompt the immune system to discard beta-amyloid, which is a hallmark of Alzheimer’s disease.

Although, during test on lab mice, antibodies used against beta-amyloid have successfully cleared plaques and reversed cognitive loss, clinical trials showed side effects that caused inflammation in the brain of Alzheimer’s patients, especially ARIA (amyloid-related imaging abnormalities). ARIA causes small bleeding and threatening brain swelling.

The research team, led by Dr. Jessica Teeling, Associate Professor in Immunology at The Centre for Biological Sciences, engineered 3 antibodies to alter the process by which they engage cells in immune system. They discovered that small, explicit alterations in the anti-amyloid antibodies maintained the immunotherapeutic activity but didn’t have any inflammatory side effects.

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Dr. Teeling says it is crucial to learn more from studying these novel interventions and optimize their effects by using antibody engineering.

The findings of the study which was in collaboration with Lundbeck (a multinational pharmaceutical company based in Denmark), underscore the possibility of antibodies to terminate disease-causing plaques and suggest possible future treatments.

The researchers believe that further work should be done to increase potency of the antibody, but without the inflammatory side effects.

These studies give us a roadmap of how to use the advancements of antibody engineering and apply antibody therapeutics targeting various neurodegenerative diseases. In the future, Alzheimer’s drugs will possess new technologies and improvements to clear plaque buildup, while keeping unharmed other areas of the brain, concludes Dr. Stavenhagen of Lundbeck.

The study was printed in Acta Neuropathologica.

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Type 2 diabetes linked to neurofibrillary tangles found in brain cells of Alzheimer’s patients

A new study has found that people with type 2 diabetes who do not have dementia may be more prone to developing neurofibrillary tangles found in brain cells of Alzheimer’s patients. Tangles are abnormal collection of insoluble twisted fibers of a type of protein called Tau.

The study published in the journal Neurology was based on data from the US Alzheimer's Disease Neuroimaging Initiative. Scientists examined the link between type 2 diabetes and the death of brain cells and loss of connections. They also looked at the beta-amyloid plaques (protein fragment snipped from an amyloid precursor protein - APP) and protein tangles in the spinal fluid of the volunteers. Beta-amyloid plaques and neurofibrillary tangles found in brain cells of Alzheimer’s patients are the hallmark of Alzheimer’s disease described by Alois Alzheimer in 1906.

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The study involved 816 participants with an average age of 74. Of these participants, 397 individuals had mild cognitive impairment (MCI), 228 had no memory of cognitive problems, 191 were Alzheimer’s patients and 124 were diabetics.

The participants underwent MRI scan for the brain. Cerebrospinal fluid samples were taken from half of the participants to measure levels of beta-amyloid and tau – proteins that make up plaques and neurofibrillary tangles found in brain cells of Alzheimer’s patients.

The study found that the brain’s cortex of the people with type 2 diabetes were more thinning. Cortex is the area with the highest concentration of nerve cells. They also found higher levels of the protein tau in the spinal fluid of the patients with type 2 diabetes which indicated more tangles in the brain.

This study has proof that people with type 2 diabetes are at twice the risk of developing dementia, explains Dr. Velandai Srikanth, study author and an assoc. prof. at Monash University in Melbourne.

Studies like this one sought to understand how conditions such as diabetes may affect death of brain cells directly or indirectly. Since brain’s nerve cells do not restore themselves, it is really crucial to find ways to decrease brain cell death, he adds.

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However, Dr. Srikanth said that the study showed only a connection between type 2 diabetes and neurofibrillary tangles found in brain cells of Alzheimer’s patients. He wasn’t sure if type 2 diabetes was the cause. He pointed to high blood sugar and obesity which are common among people with type 2 diabetes. Other researches had linked obesity to a greater accumulation of tangles.

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“Obesity could be part of the puzzle, too …. There is an interesting body of evidence" tying obesity to tau, he explained,” said Dr. Srikanth.

Dr. Srikanth said that since the study analyzed participants’ data at only point in time, cause-and-effect association between diabetes and neurofibrillary tangles found in brain cells of Alzheimer’s patients was not determined.

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Awareness of memory problems may lessen 2 to 3 years before onset of memory loss or dementia

Researchers have found that people who develop dementia may start to lose awareness of their memory problems 2 to 3 years before memory loss or dementia starts.

Dementia is a general term for a decline in memory loss and cognitive skills with enough severity to interfere with daily life. The most common form of dementia is Alzheimer’s disease. An estimated 5.3 million Americans of all ages have Alzheimer’s. It is the sixth leading cause of death in the United States. According to Alzheimer’s Society UK, the number of Alzheimer’s patients in UK will reach 850,000 by the end of this year.  

The study done by Rush University Medical Center in Chicago was published in the journal Neurology.

The researchers also found that many memory loss or brain changes related to dementia, or pathologies are to be blamed for the deterioration in memory awareness.

Robert S. Wilson, PhD, of Chicago’s Rush University Medical Center, says that their findings suggest not being aware about one’s memory problems is an unavoidable characteristic of late-life dementia that is initiated by an accumulation of changes in the brain that are related to dementia.

Dr. Wilson, who is also a study author added that not being aware of memory loss is usual in dementia, but they never knew much about its commonness, when it develops and why some individual appear more affected than others.

Participants in the memory loss or dementia study were 2,092 adults with an average age of 76 years, who had no signs of memory loss or cognitive impairment. Researchers monitored the participants for more than 10 years. They had to take yearly tests on memory and cognitive skills. They were asked how often they found it difficult to remember things and were also told to assess their memory compared to ten years prior.

During the course of the study, 239 participants were diagnosed with dementia. In these seniors, awareness of memory problems began to drop abruptly on an average of 30 months before dementia first appeared. While results were same for all the participants, researchers were surprised to find that memory loss occurred earlier in younger participants compared to the older ones. Researchers believe that this might be because reporting was misrepresented in older people who usually expect memory loss as a usual part of aging.

Although there were distinct differences in the timing of the unawareness and the speed of its progression, almost all the people were unaware about their memory difficulties at any point in the disease, explains Dr. Wilson.

Brains of 385 subjects who died during the study period were also examined by the researchers. They assessed these brains for seven types of brain alterations that are common to dementia. They discovered that three dementia-related pathologies were linked with the speedy degeneration in memory:

1.       Tau proteins also known as tangles

2.       Infarcts (areas of brain damage)

3.       Changes in the TDP-43 protein  

As these changes in the brain build up, people fail to realize that their memory is declining.

This study highlights the usefulness of loved ones and family members asking for help from healthcare professionals and doctors getting information from family or friends during the decision making process about whether someone has dementia, since those affected by dementia may not be able to provide decisive information about the case study of their own cognition, says Dr. Wilson.

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