Depression in later life may be an early warning from the brain, appearing years before Alzheimer’s begins to affect memory and thinking A new study in JNeurosci found that faster accumulation of tau, a protein closely tied to Alzheimer’s, was associated with worsening depressive symptoms in older adults who remained cognitively healthy. Teodora Markova of [...]Diseases that cause nerve cells in the brain to die over time are known as neurodegenerative diseases. These cells, known as neurons, are vulnerable to DNA damage because they are highly active cells that require large amounts of energy. Neural DNA damage is a normal part of aging as changes to the DNA sequence, called mutations, build up over time.
Previous scientists have shown that neurons from people with the neurodegenerative diseases Alzheimer’s disease (AD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS) accumulate unusually high numbers of changes in the DNA sequence, called somatic mutations. However, researchers don’t know what causes the high number of mutations or whether the same process causes them in all 3 diseases.
To answer these questions, researchers at Boston Children’s Hospital and Harvard Medical School analyzed brain tissue from people who died with and without AD, FTD, or ALS. They compared the processes that cause DNA mutations in the 3 diseases by first accessing the DNA inside individual neurons from healthy and diseased postmortem brain tissue.
To do this, they broke apart the brain tissue and added a fluorescent marker that identified the center of each neuronal cell where DNA is housed, called its nucleus. They used a sorting machine to separate the nuclei from the rest of the cell material to access the neuron’s DNA. Using a DNA sequencing method called single-cell whole genome sequencing, the team then sequenced each neuron’s DNA to identify mutations.
They analyzed 159 neurons from people with AD, 61 neurons from people with FTD, 77 neurons from people with ALS, and 232 neurons from healthy individuals. This allowed the team to compare the number and types of DNA mutations between diseased and control (non-diseased) neurons. The researchers found that compared to the control neurons, which typically accumulate only 200 to 300 mutations over an 80-year lifespan, neurons from all 3 diseases contained an unusually high number of 2-base-pair deletions, often exceeding 1,000 mutations per cell.
When a biological process damages DNA, it leaves behind its own unique signature. By identifying these signatures, scientists can identify the biological process that likely caused the damage. Since these 2-base-pair deletions were so frequent in diseased neurons, the researchers wanted to know whether they were left behind by a biological process. The researchers used a machine learning algorithm to scan DNA sequences for recurring mutation patterns and identified a signature in neuronal DNA, which they named ID-4.
When the researchers compared the ID-4 signature with a database of previously characterized signatures, they found that it was associated with a DNA repair protein called TOP1. TOP1 temporarily cuts and rejoins DNA to relieve the tension that builds up during normal cellular activity. TOP1 typically detaches from the DNA after completing this process. However, if TOP1 fails to detach, it breaks one of the two DNA strands.
To test whether abnormal TOP1 activity was breaking the DNA, the researchers isolated DNA from control and diseased neurons. They visualized the DNA on a gel, where intact DNA forms bands while broken DNA spreads out into smears. The more fragmented the DNA is, the more intense the smear appears. Using a machine that quantified the intensity of smears, the researchers found that DNA from diseased neurons produced smears that were up to 3.2 times more intense than those from control neurons. They also found that neurons with more DNA fragmentation had more ID-4 signatures.
Based on these findings, the researchers concluded that abnormal TOP1 activity created frequent single-strand DNA breaks. They proposed that some of these breaks are repaired incorrectly, eventually leading to widespread DNA breaks in all 3 neurodegenerative diseases.
Overall, the researchers found that neurons from these 3 neurodegenerative diseases accumulated excessive DNA mutations despite differences in the disease symptoms and underlying causes. Their findings also provided evidence that abnormal TOP1 activity contributes to this mutation accumulation. Based on these findings, they stated that preventing TOP1 from becoming trapped on DNA, or improving the DNA repair process that removes trapped TOP1, could be a promising way to treat a wide range of neurodegenerative diseases.
The post Common DNA damage could cause neurodegenerative diseases appeared first on Sciworthy.
Cardiovascular health in midlife may influence mental function later in life. A person’s activity level and blood sugar in middle age may help shape how quickly thinking skills decline decades later. Research from UT Health San Antonio, the academic health center of The University of Texas at San Antonio, found that physical activity and better [...]Clearing amyloid plaques may break the chain reaction that fuels brain cell destruction in Alzheimer’s disease. One Alzheimer’s brain offered researchers something they almost never get to see: a natural side-by-side experiment. In some regions, years of anti-amyloid treatment had removed most of the sticky plaques associated with Alzheimer’s disease (AD). Those areas contained little [...]Scientists have discovered that the sleep problems seen in Alzheimer’s disease may not be caused directly by harmful protein plaques as previously believed. Instead, the brain’s own immune system may be playing a much larger role, opening the door to new treatment possibilities. Sleep problems are one of the earliest and most common symptoms of […]
The post Study Finds Hidden Cause of Sleep Issue in Alzheimer’s Disease appeared first on Knowridge Science Report.
A large British study spanning more than 70 years has found that people who experience chronic money struggles over their working lives show measurable declines in memory and processing speed by their 50s, along with signs of accelerated brain shrinkage decades later.
The post Decades of Financial Hardship Linked to Faster Brain Aging appeared first on Sci.News: Breaking Science News.
Brain immune cells appear to drive reversible sleep loss in mice with Alzheimer’s-like disease. A fire starts in one room, but instead of containing the danger, the sprinkler system floods the entire house. The response causes far more damage than the original threat. Something similar may happen in Alzheimer’s disease. Amyloid plaques, the sticky protein [...]Alzheimer’s disease is the most common form of dementia and affects millions of people worldwide. It slowly destroys memory, thinking, and the ability to carry out everyday activities. Although scientists have developed medicines that can ease some symptoms, there is still no cure, and one of the biggest challenges is that treatments do not work […]
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Scientists have identified a brain protein that may help Alzheimer’s spread, revealing a potential new target for slowing the disease’s progression. Alzheimer’s disease is closely linked to the accumulation of a toxic form of the protein Tau inside the brain. As Tau damage reaches additional brain regions, more neurons are harmed, symptoms intensify, and the [...]Even moderate amounts of walking may help protect brain function and slow changes linked to Alzheimer’s disease. New research reveals a modest amount of daily movement may help protect the brain from Alzheimer’s disease, but the apparent benefit does not involve the biological target researchers expected. Using pedometers, researchers followed nearly 300 older adults with [...]Aging appears to alter how key cerebellar neurons fire, with measurable effects on movement and coordination. Aging often brings slower movement, weaker balance, and reduced agility, but the brain changes behind these losses have been difficult to identify. McGill University researchers have now directly linked declining activity in Purkinje cells, an important type of neuron [...]Scientists are paying increasing attention to pollution that comes from vehicle tires. Unlike exhaust emissions, tiny particles released as tires wear down receive much less public attention, yet they are one of the largest sources of microplastic pollution from road traffic. As these particles mix with ozone in the air, they create a chemical called […]
The post Could a Common Road Chemical Quietly Increase Alzheimer’s Risk? appeared first on Knowridge Science Report.
Alzheimer’s disease is the most common cause of dementia, affecting millions of older adults worldwide. The disease slowly damages brain cells, causing memory loss, confusion, and problems with thinking and daily activities. Scientists know that changes in the brain begin many years before the first symptoms appear. Because of this, researchers have been searching for […]
The post A New Blood Test May Predict Alzheimer’s Risk Much Earlier appeared first on Knowridge Science Report.
A new study suggests that sleep habits may influence how certain genetic variants affect early brain and cognitive changes associated with Alzheimer’s disease. Sleep may do more than help the brain recover from a busy day. New research suggests it could also influence how certain genes shape the earliest brain changes associated with Alzheimer’s disease. [...]
Alzheimer’s disease is the most common cause of dementia, a condition that slowly destroys memory, thinking abilities, and the capacity to perform everyday tasks. As populations age around the world, Alzheimer’s disease is becoming one of the biggest public health challenges. Millions of families are already caring for loved ones with dementia, and experts expect […]
The post Why Low Blood Pressure Could Be an Overlooked Warning Sign for Alzheimer’s Disease appeared first on Knowridge Science Report.
Researchers found that an Alzheimer’s-related biomarker may influence how hormone therapy affects dementia risk. Hormone therapy is commonly used to ease menopausal symptoms, including hot flashes and night sweats. Whether it affects the risk of dementia has remained a long-running question. A new study offers another clue. It suggests that an Alzheimer’s biomarker could help [...]Alzheimer’s disease is one of the most feared illnesses of old age. It slowly damages memory, thinking, and the ability to manage everyday tasks. At first, a person may simply forget names or appointments. Over time, they may struggle to recognize loved ones, communicate clearly, or live independently. Because there is currently no cure for […]
The post A Simple Eye Photo Could Spot Alzheimer’s Risk Years Before Symptoms Appear appeared first on Knowridge Science Report.
Most people rarely think about their sense of smell or taste. The smell of fresh coffee, the taste of a favorite family recipe, or the scent of flowers are such ordinary experiences that they often go unnoticed. It is only when these senses disappear that many people realize how important they are. A new study […]
The post Losing Sense of Smell and Taste Can Be as Devastating as Parkinson’s and stroke appeared first on Knowridge Science Report.
Most people know the ketogenic diet as a popular way to lose weight. Celebrities, athletes, and people trying to improve their health have embraced the low-carbohydrate eating plan over the past decade. But scientists are increasingly discovering that the keto diet may have effects far beyond the bathroom scale. According to a new review published […]
The post This Weight-Loss Diet May Also Fight Alzheimer’s and Parkinson’s Diseases appeared first on Knowridge Science Report.
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