What determines whether an individual will develop Alzheimer's disease, and why do many with the disease's characteristic toxic amyloid accumulations in the brain never exhibit associated dementia symptoms? These perplexing questions have long puzzled researchers.
Scientists from the University of Pittsburgh School of Medicine seem to have unveiled the answer. According to their groundbreaking research published in Nature Medicine, star-shaped brain cells known as astrocytes play a crucial role in the progression of Alzheimer's disease.
By testing the blood of more than 1,000 cognitively unimpaired elderly people with and without amyloid pathology, the Pitt-led research team found that only those who had a combination of amyloid burden and blood markers of abnormal astrocyte activation, or reactivity, would progress to symptomatic Alzheimer's in the future, a critical discovery for drug development aimed at halting progression.
Alzheimer's disease is a neurodegenerative condition that causes progressive memory loss and dementia, robbing patients of many productive years of life. At the tissue level, the hallmark of Alzheimer's disease is an accumulation of amyloid plaques—protein aggregates lodged between nerve cells of the brain—and clumps of disordered protein fibers, called tau tangles, forming inside the neurons.
For many decades brain scientists believed that an accumulation of amyloid plaques and tau tangles is not only a sign of Alzheimer's disease but also its direct culprit. This assumption also led drug manufacturers to heavily invest into molecules targeting amyloid and tau, overlooking the contribution of other brain processes, such as the neuroimmune system.
Recent discoveries by groups like Pascoal's suggest that the disruption of other brain processes, such as heightened brain inflammation, might be just as important as amyloid burden itself in starting the pathological cascade of neuronal death that causes rapid cognitive decline.
In his previous research, Pascoal and his group found that brain tissue inflammation triggers the spread of pathologically misfolded proteins in the brain and is a direct cause of eventual cognitive impairment in patients with Alzheimer's disease. Now, almost two years later, researchers revealed that cognitive impairment can be predicted by a blood test.
Astrocytes are specialized cells abundant in the brain tissue. Just as other members of the glia—resident immune cells of the brain—astrocytes support neuronal cells by supplying them with nutrients and oxygen and protecting them from pathogens. But because glial cells don't conduct electricity and, at first, didn't seem to play a direct role in how neurons communicate with one another, their role in health and disease had been overlooked. The latest research from Pitt changes that.
"Astrocytes coordinate brain amyloid and tau relationship like a conductor directing the orchestra," said lead author of the study Bruna Bellaver, Ph.D., postdoctoral associate at Pitt. "This can be a game-changer to the field, since glial biomarkers, in general, are not considered in any main disease model."
Scientists tested blood samples from participants in three independent studies of cognitively unimpaired elderly people for biomarkers of astrocyte reactivity—glial fibrillary acidic protein, or GFAP—along with the presence of pathological tau. The study showed that only those who were positive for both amyloid and astrocyte reactivity showed evidence of progressively developing tau pathology, indicating a predisposition to clinical symptoms of Alzheimer's disease.
The findings have direct implications for future clinical trials for Alzheimer's drug candidates. In aiming to halt disease progression sooner, trials are moving to earlier and earlier stages of pre-symptomatic disease, making correct early diagnosis of Alzheimer's risk critical for success. Because a significant percentage of amyloid-positive individuals will not progress to clinical forms of Alzheimer's, amyloid positivity alone is not enough to determine an individual's eligibility for therapy.
Inclusion of astrocyte reactivity markers, such as GFAP, in the panel of diagnostic tests will allow for improved selection of patients who are likely to progress to later stages of Alzheimer's and, therefore, help fine-tune the selection of candidates for therapeutic interventions who are more likely to benefit.
News
AI Is Overheating. This New Technology Could Be the Fix
Engineers have developed a passive evaporative cooling membrane that dramatically improves heat removal for electronics and data centers Engineers at the University of California San Diego have created an innovative cooling system designed to greatly enhance [...]
New nanomedicine wipes out leukemia in animal study
In a promising advance for cancer treatment, Northwestern University scientists have re-engineered the molecular structure of a common chemotherapy drug, making it dramatically more soluble and effective and less toxic. In the new study, [...]
Mystery Solved: Scientists Find Cause for Unexplained, Deadly Diseases
A study reveals that a protein called RPA is essential for maintaining chromosome stability by stimulating telomerase. New findings from the University of Wisconsin-Madison suggest that problems with a key protein that helps preserve chromosome stability [...]
Nanotech Blocks Infection and Speed Up Chronic Wound Recovery
A new nanotech-based formulation using quercetin and omega-3 fatty acids shows promise in halting bacterial biofilms and boosting skin cell repair. Scientists have developed a nanotechnology-based treatment to fight bacterial biofilms in wound infections. The [...]
Researchers propose five key questions for effective adoption of AI in clinical practice
While Artificial Intelligence (AI) can be a powerful tool that physicians can use to help diagnose their patients and has great potential to improve accuracy, efficiency and patient safety, it has its drawbacks. It [...]
Advancements and clinical translation of intelligent nanodrugs for breast cancer treatment
A comprehensive review in "Biofunct. Mater." meticulously details the most recent advancements and clinical translation of intelligent nanodrugs for breast cancer treatment. This paper presents an exhaustive overview of subtype-specific nanostrategies, the clinical benefits [...]
It’s Not “All in Your Head”: Scientists Develop Revolutionary Blood Test for Chronic Fatigue Syndrome
A 96% accurate blood test for ME/CFS could transform diagnosis and pave the way for future long COVID detection. Researchers from the University of East Anglia and Oxford Biodynamics have created a highly accurate [...]
How Far Can the Body Go? Scientists Find the Ultimate Limit of Human Endurance
Even the most elite endurance athletes can’t outrun biology. A new study finds that humans hit a metabolic ceiling at about 2.5 times their resting energy burn. When ultra-runners take on races that last [...]
World’s Rivers “Overdosing” on Human Antibiotics, Study Finds
Researchers estimate that approximately 8,500 tons of antibiotics enter river systems each year after passing through the human body and wastewater treatment processes. Rivers spanning millions of kilometers across the globe are contaminated with [...]
Yale Scientists Solve a Century-Old Brain Wave Mystery
Yale scientists traced gamma brain waves to thalamus-cortex interactions. The discovery could reveal how brain rhythms shape perception and disease. For more than a century, scientists have observed rhythmic waves of synchronized neuronal activity [...]
Can introducing peanuts early prevent allergies? Real-world data confirms it helps
New evidence from a large U.S. primary care network shows that early peanut introduction, endorsed in 2015 and 2017 guidelines, was followed by a marked decline in clinician-diagnosed peanut and overall food allergies among [...]
Nanoparticle blueprints reveal path to smarter medicines
Lipid nanoparticles (LNPs) are the delivery vehicles of modern medicine, carrying cancer drugs, gene therapies and vaccines into cells. Until recently, many scientists assumed that all LNPs followed more or less the same blueprint, [...]
How nanomedicine and AI are teaming up to tackle neurodegenerative diseases
When I first realized the scale of the challenge posed by neurodegenerative diseases, such as Alzheimer's, Parkinson's disease and amyotrophic lateral sclerosis (ALS), I felt simultaneously humbled and motivated. These disorders are not caused [...]
Self-Organizing Light Could Transform Computing and Communications
USC engineers have demonstrated a new kind of optical device that lets light organize its own route using the principles of thermodynamics. Instead of relying on switches or digital control, the light finds its own [...]
Groundbreaking New Way of Measuring Blood Pressure Could Save Thousands of Lives
A new method that improves the accuracy of interpreting blood pressure measurements taken at the ankle could be vital for individuals who are unable to have their blood pressure measured on the arm. A newly developed [...]
Scientist tackles key roadblock for AI in drug discovery
The drug development pipeline is a costly and lengthy process. Identifying high-quality "hit" compounds—those with high potency, selectivity, and favorable metabolic properties—at the earliest stages is important for reducing cost and accelerating the path [...]
