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
Scientists Unlock a New Way to Hear the Brain’s Hidden Language
Scientists can finally hear the brain’s quietest messages—unlocking the hidden code behind how neurons think, decide, and remember. Scientists have created a new protein that can capture the incoming chemical signals received by brain [...]
Does being infected or vaccinated first influence COVID-19 immunity?
A new study analyzing the immune response to COVID-19 in a Catalan cohort of health workers sheds light on an important question: does it matter whether a person was first infected or first vaccinated? [...]
We May Never Know if AI Is Conscious, Says Cambridge Philosopher
As claims about conscious AI grow louder, a Cambridge philosopher argues that we lack the evidence to know whether machines can truly be conscious, let alone morally significant. A philosopher at the University of [...]
AI Helped Scientists Stop a Virus With One Tiny Change
Using AI, researchers identified one tiny molecular interaction that viruses need to infect cells. Disrupting it stopped the virus before infection could begin. Washington State University scientists have uncovered a method to interfere with a key [...]
Deadly Hospital Fungus May Finally Have a Weakness
A deadly, drug-resistant hospital fungus may finally have a weakness—and scientists think they’ve found it. Researchers have identified a genetic process that could open the door to new treatments for a dangerous fungal infection [...]
Fever-Proof Bird Flu Variant Could Fuel the Next Pandemic
Bird flu viruses present a significant risk to humans because they can continue replicating at temperatures higher than a typical fever. Fever is one of the body’s main tools for slowing or stopping viral [...]
What could the future of nanoscience look like?
Society has a lot to thank for nanoscience. From improved health monitoring to reducing the size of electronics, scientists’ ability to delve deeper and better understand chemistry at the nanoscale has opened up numerous [...]
Scientists Melt Cancer’s Hidden “Power Hubs” and Stop Tumor Growth
Researchers discovered that in a rare kidney cancer, RNA builds droplet-like hubs that act as growth control centers inside tumor cells. By engineering a molecular switch to dissolve these hubs, they were able to halt cancer [...]
Platelet-inspired nanoparticles could improve treatment of inflammatory diseases
Scientists have developed platelet-inspired nanoparticles that deliver anti-inflammatory drugs directly to brain-computer interface implants, doubling their effectiveness. Scientists have found a way to improve the performance of brain-computer interface (BCI) electrodes by delivering anti-inflammatory drugs directly [...]
After 150 years, a new chapter in cancer therapy is finally beginning
For decades, researchers have been looking for ways to destroy cancer cells in a targeted manner without further weakening the body. But for many patients whose immune system is severely impaired by chemotherapy or radiation, [...]
Older chemical libraries show promise for fighting resistant strains of COVID-19 virus
SARS‑CoV‑2, the virus that causes COVID-19, continues to mutate, with some newer strains becoming less responsive to current antiviral treatments like Paxlovid. Now, University of California San Diego scientists and an international team of [...]
Lower doses of immunotherapy for skin cancer give better results, study suggests
According to a new study, lower doses of approved immunotherapy for malignant melanoma can give better results against tumors, while reducing side effects. This is reported by researchers at Karolinska Institutet in the Journal of the National [...]
Researchers highlight five pathways through which microplastics can harm the brain
Microplastics could be fueling neurodegenerative diseases like Alzheimer's and Parkinson's, with a new study highlighting five ways microplastics can trigger inflammation and damage in the brain. More than 57 million people live with dementia, [...]
Tiny Metal Nanodots Obliterate Cancer Cells While Largely Sparing Healthy Tissue
Scientists have developed tiny metal-oxide particles that push cancer cells past their stress limits while sparing healthy tissue. An international team led by RMIT University has developed tiny particles called nanodots, crafted from a metallic compound, [...]
Gold Nanoclusters Could Supercharge Quantum Computers
Researchers found that gold “super atoms” can behave like the atoms in top-tier quantum systems—only far easier to scale. These tiny clusters can be customized at the molecular level, offering a powerful, tunable foundation [...]
A single shot of HPV vaccine may be enough to fight cervical cancer, study finds
WASHINGTON -- A single HPV vaccination appears just as effective as two doses at preventing the viral infection that causes cervical cancer, researchers reported Wednesday. HPV, or human papillomavirus, is very common and spread [...]
