- Reactive astrocytes, a type of brain cell, could help scientists understand why some people with healthy cognition and amyloid-β deposits in their brains do not develop other signs of Alzheimer’s, such as tangled tau proteins.
- A study with over 1,000 participants looked at biomarkers and found that amyloid-β was only linked to increased levels of tau in individuals who had signs of astrocyte reactivity.
- The findings suggest that astrocytes are important for connecting amyloid-β with the early stages of tau pathology, which could change how we define early Alzheimer’s disease.
The accumulation of amyloid plaques and tangled tau proteins in the brain has long been considered the primary cause of Alzheimer’s disease (AD).
Drug development has tended to focus on targeting amyloid and tau, neglecting the potential role of other brain processes, such as the neuroimmune system.
Now, new research from the University of Pittsburgh School of Medicine suggests that astrocytes, which are star-shaped brain cells, play a crucial role in determining the progression of Alzheimer’s.
Astrocytes are abundant in brain tissue. Alongside other glial cells, the brain’s resident immune cells, astrocytes support neurons by providing them with nutrients, oxygen, and protection against pathogens.
Previously the role of astrocytes in neuronal communication had been overlooked since glial cells do not conduct electricity like neurons. But the University of Pittsburg study challenges this notion and sheds light on the critical role of astrocytes in brain health and disease.
The findings were recently published in Nature Medicine.
Abnormal astrocytes may indicate Alzheimer’s
Previous research suggests that disruptions in brain processes beyond amyloid burden, such as increased brain inflammation, may play a crucial role in initiating the pathological sequence of neuronal death that leads to rapid cognitive decline in Alzheimer’s.
In this new study, researchers conducted blood tests on 1,000 participants from three separate studies involving cognitively healthy older adults with and without amyloid buildup.
They analyzed the blood samples to assess biomarkers of astrocyte reactivity, specifically glial fibrillary acidic protein (GFAP), in combination with the presence of pathological tau.
The researchers discovered that only those who had both amyloid burden and blood markers indicating abnormal astrocyte activation or reactivity were likely to develop symptomatic Alzheimer’s in the future.
Dr. Tharick Pascoal, PhD, senior author of the study and associate professor of psychiatry and neurology at the University of Pittsburgh School of Medicine told Medical News Today:
“The abnormal reactivity of a group of brain cells called astrocytes is crucial to patients [who] develop Alzheimer’s disease. This brain cell abnormality can be measured with a simple blood test, enabling us to identify cognitively healthy individuals at risk of developing Alzheimer’s disease.”
Dr. Keith Vossel, professor of neurology and director of the Mary S. Easton Center for Research and Care at the University of California, Los Angeles, not involved in the research, told MNT that “once considered glue-like cells, astrocytes have many important functions in the brain, including immune functions and regulating brain activity.”
“Astrocytes increase in number and change their activity in response to brain injury or infection. This is called astrocyte reactivity,” Dr. Vossel explained.
Implications for future clinical trial development
The study findings carry significant implications for future clinical trials of potential Alzheimer’s drugs.
As trials aim to intervene at earlier stages of the disease to halt its progression, accurate early diagnosis of Alzheimer’s risk becomes crucial for successful outcomes.
Since a significant proportion of individuals with amyloid deposits will not develop clinical Alzheimer’s, amyloid positivity alone is insufficient for determining eligibility for therapy.
By incorporating astrocyte reactivity markers like GFAP into the diagnostic tests, the selection of individuals who are more likely to progress to later stages of Alzheimer’s could be improved.
“[This study] supports GFAP as a useful blood test to predict future progression to Alzheimer’s disease in cognitively normal people who have amyloid buildup in the brain, which would be helpful for future clinical trials that select cohorts of patients at highest risk of developing Alzheimer’s. Clinical trials could select cognitively unimpaired individuals with both amyloid pathology and astrocyte reactivity, instead of only amyloid pathology, to test anti-amyloid therapies and prevent progression to dementia.”
– Dr. Tharick Pascoal, PhD, senior study author
Risk estimate for cognitive decline may improve
Refining the selection process for clinical trials could aid in identifying candidates for therapeutic interventions who are more likely to benefit from the treatments.
“Our study suggests that combining therapies targeting both amyloid pathology and astrocyte reactivity could enhance the therapeutic effect,” Dr. Pascoal said.
Dr. David A. Merrill, PhD, an adult and geriatric psychiatrist and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center in Santa Monica, CA, not involved in the study, agreed.
“It could be valuable to add plasma GFAP status as a peripheral biomarker of astrocyte reactivity in the brain,” Dr. Merrill said.
“Measuring astrocyte reactivity improves our ability to estimate the risk of cognitive decline. This could help target treatment to those most likely to decline without intervention.”
Further astrocyte research still needed
While the identification of a potential new biomarker for Alzheimer’s disease is an important development, more research is still needed.
“Further studies are needed to assess peripheral GFAP as a measure of response to interventions aimed at preventing progression of the earliest stages of Alzheimer’s,” Dr. Merrill noted.
“If changes in GFAP levels tie closely to cognitive outcomes, then this new marker becomes valuable as a tool to know when we have intervened enough to make a difference. If GFAP levels are still elevated, we may need to do more to prevent AD in the individual.
– Dr. David A. Merrill, PhD, adult and geriatric psychiatrist
Dr. Vossel said that one important limitation of the study is that most of the participants identified as white and that limited demographic information was provided.
Despite this limitation, Dr. Vossel noted that “although causality between astrocyte reactivity and tau pathology was not proven, the study is important because it suggests astrocyte reactivity intervention could help prevent Alzheimer’s.”
Dr. Pascoal concluded that “in a near future, the combination of biomarkers for amyloid pathology and astrocyte reactivity (GFAP) could be used in clinical practice to identify elderly patients at risk of progressing to Alzheimer’s dementia.”
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