- 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 disease, such as entangled 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 showed signs of astrocyte reactivity.
- Findings suggest 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, overlooking 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 disease.
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 Pittsburgh study challenges that notion and sheds light on the critical role of astrocytes in brain health and disease.
The results were recently published in natural medicine.
Previous research suggests that disruptions of brain processes beyond amyloid load, such as increased brain inflammation, may play a crucial role in triggering the pathological sequence of neuronal death that leads to decline. rapid cognition in Alzheimer’s disease.
In this new study, researchers performed blood tests on 1,000 participants from three separate studies involving cognitively healthy older adults with and without amyloid buildup.
They analyzed blood samples to assess biomarkers of astrocyte reactivity, specifically glial fibrillary acidic protein (GFAP), in combination with the presence of pathological tau.
The researchers found that only those who had both an amyloid load and blood markers indicating abnormal astrocyte activation or reactivity were likely to develop symptomatic Alzheimer’s disease in the future.
Dr. Tharick PascoalPhD, lead study author and associate professor of psychiatry and neurology at the University of Pittsburgh School of Medicine said Medical News Today:
“The abnormal reactivity of a group of brain cells called astrocytes is crucial for patients (who) develop Alzheimer’s disease. This brain cell abnormality can be measured with a simple blood test, allowing us to identify cognitively healthy individuals at risk of developing Alzheimer’s disease.
Dr. Keith Vosselprofessor 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, said DTM that “once thought of as glue-like cells, astrocytes have many important functions in the brain, including immune functions and the regulation of 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.
The results of the study have important implications for future clinical trials of potential drugs for Alzheimer’s disease.
While trials aim to intervene at early stages of the disease to halt its progression, accurate early diagnosis of Alzheimer’s risk becomes crucial for positive outcomes.
Since a significant proportion of individuals with amyloid deposits will not develop clinical Alzheimer’s disease, amyloid positivity alone is insufficient to determine eligibility for therapy.
By incorporating astrocyte reactivity markers like GFAP into diagnostic tests, the selection of people most likely to progress to later stages of Alzheimer’s disease could be improved.
“(This study) supports GFAP as a useful blood test to predict future progression of Alzheimer’s disease in cognitively normal people who have amyloid accumulation in the brain, which would be useful for future clinical trials. that would select cohorts of patients most at risk of developing Alzheimer’s disease. Clinical trials could select individuals without cognitive impairments 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, lead study author
Refining the selection process for clinical trials could help identify candidates for therapeutic interventions most likely to benefit from treatments.
“Our study suggests that combining therapies targeting both amyloid pathology and astrocyte reactivity could enhance therapeutic effect,” Dr. Pascoal said.
Dr. David A. Merrill, PhD, an adult and geriatric psychiatrist and director of the Pacific Brain Health Center at the Pacific Neuroscience Institute in Santa Monica, Calif., not involved in the study, agreed.
“It might be useful to add plasma GFAP status as a peripheral biomarker of astrocyte responsiveness in the brain,” Dr. Merrill said.
“Measuring astrocyte responsiveness improves our ability to estimate the risk of cognitive decline. This could help target treatment to those most likely to decline without intervention.
While the identification of a potential new biomarker for Alzheimer’s disease is an important development, further research is still needed.
“Further studies are needed to evaluate peripheral GFAP as a measure of response to interventions aimed at preventing the progression of the early stages of Alzheimer’s disease,” Dr. Merrill noted.
“If changes in GFAP levels are closely linked to cognitive outcomes, then this new marker becomes a valuable tool for knowing when we have intervened enough to make a difference. If GFAP levels are still high, we may need to do more to prevent AD in the individual.
– Dr. David A. Merrill, PhD, adult and geriatric psychiatrist
Dr. Vossel said an important limitation of the study is that most participants self-identified as white and limited demographic information was provided.
Despite this limitation, Dr. Vossel noted that “although causation between astrocyte reactivity and tau pathology has not been proven, the study is important because it suggests that intervention in astrocyte reactivity could help to prevent Alzheimer’s disease.
Dr. Pascoal concluded that “in the near future, the combination of biomarkers of amyloid pathology and astrocyte reactivity (GFAP) could be used in clinical practice to identify elderly patients at risk of progressing to dementia of Alzheimer’s”.