Reviewed by the Help Dementia Editorial Team — our editors review every article for accuracy against guidance from the National Institute on Aging, the Alzheimer’s Association, and peer-reviewed sources.
Brain cell sits at the center of this dementia and brain health question.
Brain cell support systems—particularly the non-neuronal cells that surround and protect neurons—are emerging as a critical frontier in Alzheimer’s disease treatment. Rather than focusing exclusively on amyloid plaques and tangles, researchers are increasingly targeting the brain’s supporting cast: astrocytes and microglia, the immune-like cells that manage the inflammatory environment around neurons. This shift represents a fundamental change in how we approach Alzheimer’s treatment, with nearly 200 clinical trials currently underway assessing more than 150 novel drugs that target various pathways involved in neurodegeneration, including several directed at these brain cell support systems. The significance of this approach lies in understanding that Alzheimer’s disease isn’t solely a disease of the neurons themselves.
The cells surrounding neurons—astrocytes, microglia, and other glial cells—play essential roles in maintaining brain health, clearing cellular debris, and regulating inflammation. When these support systems malfunction, they can paradoxically accelerate neuronal damage rather than prevent it. Mount Sinai researchers recently discovered that reactive astrocytes control the spacing around amyloid plaques, directly affecting how other brain cells can access and clear these harmful deposits. This single discovery opened an entirely new therapeutic avenue: instead of just attacking plaques directly, scientists can now target the support cells to make the brain’s natural cleanup processes more efficient.
Table of Contents
- How Are Researchers Targeting Brain Cell Support Systems in Alzheimer’s?
- The Role of Astrocytes in Clearing Alzheimer’s Pathology
- Microglial Activation and the Neuroinflammation Connection
- The Current State of Clinical Development: From Laboratory Promise to Patient Care
- Limitations and Safety Considerations in Brain Cell Manipulation
- Astrocyte Research at Mount Sinai and Beyond
- The Future of Multi-Target and Combination Therapies
- Conclusion
How Are Researchers Targeting Brain Cell Support Systems in Alzheimer’s?
The therapeutic landscape has diversified dramatically. Among the 150+ drugs currently in clinical trials, 24 agents are specifically addressing neuroinflammation and immune processes—essentially targeting the dysregulated behavior of brain support cells. Another 30 drugs target neurotransmitter receptors, 25 address amyloid-beta pathophysiology, 15 focus on tau-related processes, and 9 tackle synaptic plasticity and neuroprotection. This distribution shows that researchers are no longer putting all eggs in one basket.
One particularly promising candidate is NLY01, an engineered version of exedin-4 that acts as a glucagon-like peptide-1 receptor agonist. In laboratory models of Alzheimer’s disease, NLY01 selectively blocks the harmful activation of microglia—the brain’s resident immune cells—while simultaneously inhibiting the formation of reactive astrocytes. Critically, the drug preserves neurons in these experimental models, suggesting a protective mechanism rather than a destructive one. This represents a major conceptual shift: instead of treating support cells as mere bystanders, researchers are designing drugs that harness their natural protective functions.
The Role of Astrocytes in Clearing Alzheimer’s Pathology
Astrocytes have long been understudied in Alzheimer’s research, despite their abundance in the brain. These star-shaped cells outnumber neurons and perform countless essential functions: they regulate blood flow, provide nutrients, maintain proper ion balance, and control the inflammatory environment. When astrocytes become “reactive”—a stressed state triggered by neurodegeneration—they can become part of the problem rather than the solution. Reactive astrocytes gather around amyloid plaques, but their presence can actually create a physical barrier that prevents other cleanup cells from accessing and clearing the plaques. Mount Sinai researchers identified the protein plexin-B1 as a key controller of this astrocyte behavior. By manipulating plexin-B1, they demonstrated in laboratory studies that they could enhance the brain’s natural ability to clear amyloid plaques.
However, a critical limitation remains: this research is still largely confined to animal models. The translation to human patients will require careful clinical trials to ensure the approach is both safe and effective in the living human brain, where astrocyte behavior may differ from laboratory conditions. Additional research has focused on the CaN/NFAT pathway within astrocytes. When researchers inhibited this pathway in APP/PS1 mouse models of Alzheimer’s disease, they observed two important outcomes: astrogliosis (the harmful proliferation of astrocytes) slowed, and cognitive function improved. Yet this approach also carries a caveat: blocking pathways in the brain can have unintended consequences on normal cellular functions. Complete pathway shutdown might sacrifice beneficial astrocyte activities while eliminating harmful ones, creating a narrow therapeutic window.
Microglial Activation and the Neuroinflammation Connection
Microglia are the brain’s immune cells, constantly patrolling the nervous system and removing dead cells, pathogens, and misfolded proteins. In healthy brains, this process is tightly controlled. In Alzheimer’s disease, however, microglia become chronically activated, releasing inflammatory molecules that can damage nearby neurons rather than protect them. This overactivation is a hallmark of Alzheimer’s pathology, and it’s why microglia-targeted therapies have attracted intense research attention. A 2025 update on treatment strategies for the Alzheimer’s disease spectrum confirms glial-targeted therapeutics as a major emerging therapeutic direction.
The convergence of evidence from multiple research centers—including Frontiers in Neuroscience, PMC databases, and academic medical centers—suggests that the field has reached a turning point. Neuroinflammation is now widely recognized as not just a consequence of Alzheimer’s pathology, but as an active driver of neuronal loss. This distinction matters clinically because it means controlling microglial activation might slow disease progression, not just manage symptoms. NLY01 represents one strategy for achieving this control: it suppresses the harmful activation of microglia through glucagon-like peptide-1 receptors, essentially telling overactive immune cells to calm down. But the strategy also highlights a fundamental challenge in treating neuroinflammation: the same inflammatory response that causes damage is also necessary for some brain functions, including learning and memory formation. Overly suppressing microglial function could theoretically impair normal cognitive processes, making the therapeutic window narrow and the need for precise dosing critical.
The Current State of Clinical Development: From Laboratory Promise to Patient Care
Most glial-targeted approaches remain in preclinical animal model testing, with only limited human clinical trials currently underway. This gap between laboratory success and clinical reality represents both the promise and the challenge of this emerging field. Researchers have demonstrated proof-of-concept in mice and cell cultures, but the complexity of the human brain—with its billions of neurons and trillions of connections—presents obstacles that no animal model can fully capture. The distinction between therapeutic approaches matters in practice.
Among the 150+ drugs currently being tested, the majority are still in early phases of clinical development. This means patients with Alzheimer’s disease today have limited access to glial-targeted therapies and must rely primarily on existing treatments like aducanumab and lecanemab, which target amyloid plaques directly. However, the robust pipeline of 200 clinical trials suggests that new options will emerge within the next few years, potentially offering alternatives or combinations with existing therapies. One important comparison: while anti-amyloid monoclonal antibodies like lecanemab have shown modest cognitive benefits in early-stage disease, they also carry risks of amyloid-related imaging abnormalities (ARIA)—brain microhemorrhages and microinfarcts detected on MRI. Glial-targeted approaches theoretically might avoid these complications since they work through different mechanisms, but this potential advantage remains theoretical until human trials provide concrete data.
Limitations and Safety Considerations in Brain Cell Manipulation
Manipulating brain cell function carries inherent risks that extend beyond laboratory models. The brain is an exquisitely balanced system where inflammation, clearance of debris, and protective functions must all occur in precise proportion. Push one lever too hard, and you risk disrupting another. For example, while blocking harmful microglial activation sounds beneficial, microglia also perform essential housekeeping functions: they prune unnecessary synapses during learning, eliminate pathogens, and support neuronal survival. Overblocking microglial function could theoretically impair these beneficial processes. Another limitation involves the blood-brain barrier, the selective membrane that protects the brain but also prevents many therapeutic molecules from entering. Most drugs for Alzheimer’s must cross this barrier to reach affected brain tissue, and not all candidate compounds do so effectively.
This means promising laboratory results sometimes fail to translate clinically because the drug never reaches its intended target in sufficient concentration. The researchers working on NLY01 and other glial-targeted agents must overcome this fundamental challenge alongside the biological challenges of the disease itself. The heterogeneity of Alzheimer’s disease itself presents an additional complication. Not all Alzheimer’s cases follow the same pathological pattern. Some patients have primarily tau pathology with minimal amyloid, others show mixed patterns, and still others present with atypical variants. A glial-targeted therapy that works brilliantly for one patient might be ineffective for another depending on the underlying pathology. This means future treatment will likely require better biomarkers and diagnostic tests to match patients with the most appropriate therapies.
Astrocyte Research at Mount Sinai and Beyond
The Mount Sinai discovery regarding plexin-B1 and astrocyte spacing illustrates how detailed cellular biology can translate into therapeutic opportunity. By studying how astrocytes arrange themselves around amyloid plaques, researchers uncovered a physical problem that could be solved with pharmacological intervention. The research pathway—from basic cell biology observation to therapeutic target identification—took years and required expertise spanning molecular biology, neurology, and translational medicine.
Expanding this work globally, multiple research teams are now investigating how to modulate astrocyte behavior through different molecular targets. Some focus on reducing astrocyte reactivity, others on enhancing specific protective functions, and still others on preventing the formation of scars that can impede neuronal repair. This diversity of approaches increases the probability that at least some will prove effective in human patients, even if others fall by the wayside during clinical development.
The Future of Multi-Target and Combination Therapies
The future of Alzheimer’s treatment likely involves combinations rather than single-agent approaches. A patient might eventually receive an anti-amyloid monoclonal antibody alongside a microglial-targeting agent and an astrocyte-modulating drug, each attacking different aspects of the disease simultaneously. This polypharmacy approach mirrors successful cancer treatment strategies, where combinations of targeted drugs often outperform any single agent alone.
The pipeline of nearly 200 clinical trials testing over 150 novel drugs suggests we are entering an era of unprecedented therapeutic diversity for Alzheimer’s disease. Within the next five to ten years, clinicians will likely have access to drugs targeting multiple pathways simultaneously, allowing for personalized treatment plans based on individual patient pathology. The brain cell support systems—astrocytes, microglia, and other glial cells—will almost certainly play a central role in these emerging treatment strategies.
Conclusion
Brain cell support systems represent a fundamental shift in how researchers and clinicians approach Alzheimer’s disease treatment. Rather than exclusively targeting amyloid plaques or tau tangles, emerging therapies are learning to work with and through the brain’s supporting cells to enhance natural protective and clearance mechanisms. With nearly 200 clinical trials currently assessing over 150 novel drugs—including multiple candidates targeting neuroinflammation and glial cell function—the therapeutic landscape is diversifying rapidly.
The research from Mount Sinai on astrocyte spacing, the development of glial-targeting candidates like NLY01, and the confirmation of glial-targeted therapeutics as a major emerging direction all point toward a new era in Alzheimer’s care. The translation from laboratory success to clinical benefit remains challenging, and most glial-targeted approaches are still in preclinical or early clinical stages. However, the convergence of evidence, the robust clinical trial pipeline, and the fundamental logic of the approach suggest that these therapies will become part of standard Alzheimer’s treatment within the coming years. For patients and families facing dementia, this represents genuine hope—not from marketing hype, but from the steady progress of scientific research aimed at understanding and restoring the brain’s own healing mechanisms.
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For more, see CDC — Alzheimer’s and Dementia.
