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 Have Discovered Toxic “Forever Chemicals” in Bottled Water
Scientists have found toxic PFAS in drinking water samples from around the world, with higher levels in tap water from China compared to the UK. Boiling water or using a filtration jug can reduce [...]
Urban Microbes Are Eating Disinfectants – Are We Fueling a New Health Threat?
New research reveals that microbes in urban environments are evolving to withstand the very cleaning agents designed to eliminate them. The study also uncovers new strains in Hong Kong, previously only found in the [...]
Startling Study Shows High-Potency Cannabis Alters DNA
The study shows that frequent use of high-potency cannabis alters DNA, affecting genes related to energy and immune function. These changes differ between those with and without psychosis, suggesting cannabis use could influence mental health through biological [...]
New nanotherapy targets artery inflammation in cardiovascular disease
Inflammation of the arteries is a primary precursor and driver of cardiovascular disease—the No. 1 killer of people in the United States. This inflammation is associated with the buildup of dangerous plaque inside the [...]
Revolutionary Nanoparticle Therapy for Prostate Cancer
A groundbreaking research effort involving teams from the University of Virginia, Mount Sinai, the University of Michigan, the University of Texas, and others has displayed the clinical efficacy of an innovative therapy that utilizes nanoparticles and [...]
Antibody engineering drives innovation in drug development
Monoclonal antibodies (mAbs) are used to prevent, detect, and treat a broad spectrum of non-communicable and communicable diseases. Over the past few years, the market for mAbs has grown exponentially with an expected compound [...]
Breakthrough Study Reveals How Bladder Cancer Starts and Spreads
Researchers found that DNA mutations from antiviral enzymes and chemotherapy fuel early bladder cancer, while abnormal circular DNA in tumor cells drives resistance to therapy. These discoveries open new therapeutic avenues. A groundbreaking study led by [...]
AI and Quantum Mechanics Accelerate Drug Discovery
A recent article published in the Journal of Chemical Information and Modeling researchers at Southern Methodist University (SMU) have developed SmartCADD, an open-source virtual tool designed to speed [...]
Targeting ‘undruggable’ diseases: Researchers reveal new levels of detail in targeted protein degradation
Researchers at the University of Dundee have revealed in the greatest detail yet the workings of molecules called protein degraders which can be deployed to combat what have previously been regarded as "undruggable" diseases, [...]
Revolutionizing Virology: AI Discovers Over 160,000 New RNA Viruses
Largest discovery of new virus species sheds light on the hidden virosphere. Artificial intelligence (AI) has been used to reveal details of a diverse and fundamental branch of life living right under our feet and in every [...]
Cardiac Crisis: COVID-19 Doubles Risk of Heart Attacks, Strokes, and Death
Research indicates that COVID-19 survivors face doubled risks of severe cardiac events for years after recovery, especially if hospitalized. People with A, B, or AB blood types are particularly vulnerable, highlighting the need for personalized approaches [...]
AI steps into science limelight with Nobel wins
For long periods of its history, artificial intelligence has lurked in the hinterland of science, often unloved and unfunded—but two Nobel prizes in one week suggest its time in the sunshine has finally arrived. [...]
MIT Scientists Shed New Light on the Critical Brain Connections That Define Consciousness
A new study provides further evidence that consciousness depends on communication between the brain’s sensory and cognitive regions in the cortex. Our brains are constantly making predictions about our surroundings, enabling us to focus [...]
Common Chemicals Found in Shampoo and Plastic Could Be Quietly Disrupting Your Heart’s Rhythm
UC study of Fernald data links environmental phenols to heart toxicities Environmental phenols are present in numerous everyday consumer products, serving as preservatives in packaged foods, parabens in shampoos, and bisphenol A (BPA) in [...]
Revolutionary Brain Tech Offers New Hope for Stroke and Injury Recovery
University of Pittsburgh researchers report that deep brain stimulation (DBS) can effectively enhance motor functions in individuals with arm and hand paralysis due to brain injuries, with promising results from early human and monkey [...]
NIH Scientists Discover Gene Responsible for Rare Eye Disease
Findings supported by the NIH pave the way for the development of genetic testing, clinical trials, and therapies. Researchers at the National Institutes of Health (NIH) and their collaborators have discovered a gene linked to certain [...]