Health
New Alzheimer’s research reveals ‘quiet’ phase of the disease, before symptoms appear
New details have emerged about how Alzheimer’s disease affects the brain.
Researchers led by the Allen Institute for Brain Science in Seattle and University of Washington Medicine have identified cellular changes in the brains of people with the disease — and a timeline of when they occur.
“Instead of looking at AD just through the usual lens of plaques and tangles, we focused on how specific cell types were changed in each phase,” study author Dr. Kyle Travaglini, Ph.D., a scientist at Allen Institute, told Fox News Digital via email.
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“We identified two main phases in AD by arranging donors along a continuous disease trajectory — a slow, early phase with low levels of pathology and no cognitive decline, followed by a later phase where there’s a huge buildup of pathology and cognitive decline.”
Researchers examine donated brain tissue samples through a microscope in a lab at the Allen Institute. (Allen Institute for Brain Science)
The study, which was published this week in Nature Neuroscience, examined millions of cells from the donated brain tissue of 84 deceased Alzheimer’s patients.
The donors ranged from mild cases with no symptoms to advanced dementia cases.
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“By studying research subjects across the spectrum of AD, including those in the earliest stages of disease, we hope to identify vulnerable cells early in the disease process, long before a person develops symptoms,” C. Dirk Keene, professor of neuropathology at UW Medicine, said in a press release.
Researchers focused on the middle temporal gyrus (MTG) — the part of the brain that controls language, memory and vision.
That portion of the brain is known as a “critical transition zone,” where evidence of Alzheimer’s appears and then worsens as the disease progresses.
A scientist creates a sample in the lab at the Allen Institute. (Allen Institute for Brain Science)
Using machine learning technology, researchers compared the cells, genes and DNA of the Alzheimer’s brain samples to maps of the normal brain generated by the Allen Institute.
“With these tools, scientists were able to detect the earliest cellular changes to the brain to create a more complete picture of what happens over the entire course of the disease,” John Ngai, Ph.D., director of The BRAIN Initiative, said in the release.
“We created a pathology clock that tells not only what changes are happening in this cortical region, but when.”
“The new knowledge provided by this study may help scientists and drug developers around the world develop diagnostics and treatments targeted to specific stages of Alzheimer’s and other dementias,” he added.
Creating a disease timeline
The study identified “two distinct phases” of Alzheimer’s disease.
“You could say we created a pathology clock that tells not only what changes are happening in this cortical region, but when,” said Mariano Gabitto, Ph.D., a lead author and assistant investigator at the Allen Institute, in the release.
Researchers study images of brain tissue to determine Alzheimer’s-related cellular changes. (Allen Institute for Brain Science)
First, there was a “slow, early buildup of abnormal cellular changes,” the researchers noted.
During this period, the patient may not experience any symptoms of memory loss or cognitive decline.
In that first phase, the researchers were surprised to discover the loss of certain inhibitory neurons that were not previously linked to Alzheimer’s.
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Travaglini described that as a “critical discovery,” as those neurons act as “brakes” for brain activity and “keep things balanced.”
“This specificity gives us new clues about how and why certain brain circuits could break down in AD,” he said.
Researchers analyze brain tissue samples in a lab at the Allen Institute. (Allen Institute for Brain Science)
Richard J. Hodes, MD, director of the NIH National Institute on Aging, noted that one of the challenges in diagnosing and treating Alzheimer’s is that much of the damage to the brain happens in this early phase, before symptoms occur.
“The ability to detect these early changes means that, for the first time, we can see what is happening to a person’s brain during the earliest periods of the disease,” he said in the release.
“For the first time, we can see what is happening to a person’s brain during the earliest periods of the disease.”
The second phase was marked by a “much more extensive loss” of different types of neurons and cells, leading to the accumulation of the hallmark “plaques and tangles” in the brain — which is typically when patients begin to notice cognitive decline.
The bigger picture
Igor Camargo Fontana, Ph.D., Alzheimer’s Association director of scientific conference programming in Chicago, was not involved in the study but shared what he described as the “bigger picture” it revealed.
“Instead of looking at AD just through the usual lens of plaques and tangles, we focused on how specific cell types were changed in each phase,” a researcher said. (iStock)
“Alzheimer’s disease has a long pre-symptomatic period; Alzheimer’s-related changes take place in the brain 10, 15 or even 20 years before the onset of memory and thinking symptoms,” he told Fox News Digital.
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“If the findings in this new paper are confirmed by other labs, it raises the question of whether effectively addressing the brain changes that happen in what the authors call the first ‘quiet’ phase can slow, delay or prevent the second, more destructive phase.”
The hope is that this new timeline of how the disease affects the brain will help guide the development of new treatments. (iStock)
Looking ahead, Fontana says it will be important to further investigate the “quiet” phase to confirm how it’s linked to the better-known biomarkers of Alzheimer’s, such as amyloid and tau.
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The hope is that this new timeline of how the disease affects the brain will help guide the development of new treatments, according to researchers.
The study was supported by the National Institute on Aging and the NIH BRAIN Initiative.
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A new injectable therapy is showing positive results in reducing melanoma throughout a five-year period.
The personalized mRNA cancer therapy, called intismeran autogene, combined with the cancer immunotherapy drug KEYTRUDA (pembrolizumab), is a collaboration between Merck and Moderna.
The results from the phase 2b KEYNOTE-942 study were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on May 27.
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After about a five-year follow-up, the combo drug was found to reduce the risk of melanoma recurrence or death by 49% compared to pembrolizumab alone.
The researchers analyzed data from 157 patients with high-risk stage 3 and 4 melanoma whose cancer had been removed via surgery. The participants were split into two groups — one received the combo therapy and the other only received pembrolizumab, according to a press release.
The therapy was found to reduce the risk of melanoma recurrence or death by 49% compared to pembrolizumab alone after a five-year follow-up. (iStock)
The findings revealed that the combination group saw benefits that were “sustained and durable over time.”
Intismeran autogene is designed using mutations identified in a patient’s own tumor, with the intention of teaching the immune system what the cancer looks like so that it can recognize and attack it.
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According to the researchers, intismeran is “well-tolerated” with a “manageable” safety profile.
The most commonly cited side effects of the personalized mRNA vaccine plus KEYTRUDA were fatigue, injection-site pain, chills, fever and headache. The researchers reported no new long-term safety concerns and no severe vaccine-related adverse events.
The combination therapy is currently being evaluated in a phase 3 study — the final confirmation stage.
Patients with late-stage melanoma have a “significant risk” of cancer recurrence, according to an expert. (iStock)
In a Merck press release from January, Kyle Holen, MD, Moderna’s senior vice president and head of development, oncology and therapeutics, noted that this data highlights the “potential of a prolonged benefit … in patients with resected high-risk melanoma.”
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“We continue to invest in our platform in oncology because of encouraging outcomes like these, which illustrate mRNA’s potential in cancer care,” he said.
Dr. Marjorie Green, senior vice president and head of oncology, global clinical development at Merck Research Laboratories, also commented that for many patients with stage 3 or 4 melanoma, there is a “significant risk of recurrence following surgery.”
Researchers confirmed that the combination therapy is currently being evaluated in a phase 3 study. (iStock)
“As such, demonstrating the longer-term potential of intismeran autogene and KEYTRUDA to reduce the risk of recurrence for certain patients with melanoma is a meaningful milestone,” she said.
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The company cited encouraging five-year follow-up data and pointed to upcoming late-stage INTerpath trial results with Moderna in several hard-to-treat cancers.
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An accidental lab discovery has opened the door to entirely new ways of preventing the flu.
While investigating how influenza replicates, researchers discovered that different flu strains use completely different strategies to infiltrate human cells, SWNS reported.
By targeting the specific molecules the viruses rely on, scientists found that they could block them from entering new cells and halt their replication altogether.
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Researchers say these “fundamental insights” into seasonal influenza highlight a clear path toward developing better preventive medications.
“The hope is that fundamental, curiosity-based research like this helps to pave the way for novel strategies to treat and prevent influenza infections,” principal investigator Dr. Emily Bruce, from the University of Vermont’s Larner College of Medicine, said in the SWNS report.
While investigating how influenza replicates, researchers discovered that different flu strains use completely different strategies to infiltrate human cells. (iStock)
While several flu strains cause illness, H1N1 and H3N2 influenza A viruses are the most common. However, current flu tests cannot differentiate between them, and clinical treatments are identical for both.
Although vaccines and antivirals are available, Bruce noted a “dire” need for better medications to stop the virus from spreading cell to xxcell.
“You don’t get sick when a virus is in one cell,” he noted. “You get sick because a virus replicates itself and goes into many more cells.”
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The study, which was published in The Journal of Virology, originally aimed to map how viral RNA segments are transported within cells to create new viral particles.
The team used H1N1 and H3N2 viruses isolated from the nasal passages of positive patients in 2022.
Clinical treatments remain identical for both primary strains of the flu virus. (iStock)
During the investigation, the team unexpectedly stumbled upon a cellular pathway that blocked the virus from entering lung cells, SWNS reported.
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The data revealed that when a specific human protein called Rab11B was depleted, H3N2 viruses failed to enter human lung cells. H1N1 viruses were completely unaffected.
Using reverse genetics, the team mapped this defect and uncovered a brand-new, H3N2-specific role for Rab11B during viral entry.
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This discovery challenged the scientific assumption that all flu viruses enter cells the same way.
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“Viruses are like pirates from different countries hijacking someone’s ship,” Bruce said. “Different viruses, like different types of pirates, use different methods to get onboard.”
This discovery challenged the scientific assumption that all flu viruses enter cells the same way. (iStock)
“We had previously thought that all flu viruses used the same way to get into a cell, but we discovered that this is not true,” she went on. “H1N1 and H3N2 need different proteins to get in, and if you get rid of the right protein, a specific virus can’t get in.”
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While these findings identify a critical cellular pathway for viral entry, the study was conducted using isolated cells, the researchers acknowledged.
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Further research is needed to determine whether blocking the protein is safe and effective within a live, complex human respiratory system.
Bruce and the team hope to conduct further research to determine whether this Rab11B-dependency is a fundamental property of H3N2, or if it’s a trait unique to currently circulating flu strains.
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Eating processed meat like ham, sausage and bacon may be linked to a higher risk of certain types of cancer, according to new research.
While health organizations have already confirmed that processed meat can contribute to colon cancer, this study looked closer at cancers in the upper digestive tract, where the link has historically been less clear.
To understand these connections, researchers from the European Prospective Investigation into Cancer and Nutrition (EPIC), one of the world’s largest long-term nutrition and cancer cohorts, tracked the health and diets of 450,112 people across Europe for an average of 14 years.
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The study group included 131,426 men and 318,686 women, according to the study’s press release.
During the follow-up period, 876 people developed stomach cancer and 215 people developed esophageal adenocarcinoma, which is cancer of the tube connecting the mouth to the stomach.
For female participants, eating both processed meat and white meat was linked to an increased risk of developing the disease. (iStock)
Researchers tracked where the stomach cancers grew, separating them into the upper part of the stomach near the throat and the lower part of the stomach.
The researchers also sorted the tumors into two categories based on how the cancer cells appeared under a microscope: intestinal, which forms more organized structures, and diffuse, in which the cells are more scattered throughout the tissue.
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After adjusting for other lifestyle factors, the researchers found that for every extra 30 grams of processed meat a person ate per day, their overall risk of stomach cancer went up by 9%. Eating that same extra 30 grams a day was also linked to a 13% higher risk of esophageal adenocarcinoma.
A standard single slice of regular deli-sliced ham or lunch meat averages around 28 grams, according to USDA data and nutritional tracking databases.
An extra 20 grams of white meat, such as chicken and turkey, was linked to a 12% higher risk of cancer in the main body of the stomach. (iStock)
An extra 20 grams of white meat, such as chicken or turkey, was linked to a 12% higher risk of cancer in the main body of the stomach, the researchers noted.
The study also revealed differences between men and women. For male participants, only processed meat showed a clear, statistically significant link to a higher risk of stomach cancer. For female participants, however, eating both processed meat and white meat was linked to an increased risk.
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These findings align with global health benchmarks, particularly those established by the World Health Organization’s International Agency for Research on Cancer.
The agency has long classified processed meat as a known human carcinogen, primarily due to its strong, well-documented links to colorectal cancer.
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However, health organizations have also consistently pointed to a potential, yet less definitive, relationship between these meats and cancers of the stomach.
Eating 30 grams of processed meat a day, or the equivalent to one slice of ham, was linked to a 13% higher risk of esophageal adenocarcinoma. (iStock)
Further scientific investigation is needed to confirm the findings and to account for other underlying risk factors, such as certain stomach infections, which could interact with dietary habits.
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A key limitation of the study is its reliance on self-reported diets, which can sometimes lead to inaccuracies in how participants recall their meat consumption over time, the researchers noted.
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The findings were published in the International Journal of Cancer.
Fox News Digital reached out to the researchers requesting comment.
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