Written by Katharine Lang — Fact checked by Jill Seladi-Schulman, Ph.D.
Population growth and aging mean that the number of people with dementia is forecast to reach almost 152.8 million by 2050.
They clear the beta-amyloid plaques that are characteristic of Alzheimer’s, potentially delaying the cognitive symptoms. However, the treatments are expensive, and some experts are concerned that the risk of side effects may outweigh their benefits.
In a new study from Texas A & M University College of Medicine, researchers have used a nasal spray to target microglia and astrocytes — cells that cause neuroinflammation (brain inflammation) — delaying the progression of Alzheimer’s disease in a mouse model.
They suggest that, if similar effects are confirmed in people, the spray could delay Alzheimer’s progression by up to 15 years.
Courtney Kloske, PhD, Alzheimer’s Association director of scientific engagement, who was not involved in this study, told Medical News Today that its findings are encouraging but that much more research is needed to confirm them:
“Models are important in helping us understand the basic biology of the disease, but we need human studies in representative populations for ideas to be fully validated. Microglia are an incredibly complex immune cell in the brain and researchers are still working to understand why they respond the way they do at different points in disease. Therefore, while these are intriguing findings, more research is needed to understand the impacts and outcomes of this kind of intervention on people living with, or at risk for, Alzheimer’s.”
Microglia and astrocytes play a key role in neuroinflammation in Alzheimer’s disease. In healthy brains, they protect nerve cells and remove damaged nerve tissue, but in Alzheimer’s, after initially clearing beta-amyloid plaques, they become overactive and destroy nerve cells.
Using a mouse model of the early stages of Alzheimer’s disease, the researchers administered a nasal spray containing an anti-inflammatory treatment derived from stem cells in extracellular vesicles.
The aim was to target these immune cells to decrease inflammation and reduce the buildup of harmful proteins in the brain.
They gave the 3-month-old mice — both mice genetically modified to display Alzheimer’s-like symptoms (transgenic mice) and wild-type mice — 2 doses of the nasal spray containing the treatment, or a placebo spray, 1 week apart.
Seventy-two hours after the second dose, they euthanized five mice, to assess the numbers and activity of microglia and astrocytes.
Three weeks after the second treatment, they subjected the rest of the mice to a series of behavioral tests. The researchers repeated these tests regularly over the next month to monitor the mice’s cognitive function following treatment. They then euthanized the mice and analyzed their brains.
In this mouse model, untreated transgenic mice usually show characteristic signs of Alzheimer’s such as beta-amyloid plaques, increased microglial activity, and inflammation by the age of 4.5 months.
However, at 4.5 months old, the mice that received the nasal spray treatment in this study had reduced microglial clusters, as well as reduced activation of genes associated with neuroinflammation. In addition, they had fewer beta-amyloid plaques than the untreated mice.
These reduced inflammatory effects were most notable in the hippocampus — the area of the brain that plays a major role in learning and memory — which is severely affected by Alzheimer’s disease.
In behavioral tests, both male and female treated mice showed better cognitive and mood function than the untreated mice.
However, Clifford Segil, DO, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, who was not involved in this research, emphasized that this was the early days for plaque-removing treatments.
“The authors in the study noted nasal delivered stem cells could decrease the number of plaques in Alzheimer’s dementia patients and medications are being used around the world right now doing the same thing. Post-marketing surveillance is going to determine if these plaque-reducing medicines cause any noticeable cognitive improvements,” he told MNT.
“If the clinical use results in patients with improved memory, unlike the trials which resulted in these medications’ approval, novel and early methods to decrease brain plaques will be extremely desirable,” Segil added.
Reducing the activity of microglia could lead to a reduction in their beneficial effects, but this was not seen when mice were treated with the nasal spray.
In a press release, the study authors said that “an intake of neural stem cell-derived extracellular vesicles significantly changed microglia gene expression and reduced the multiple harmful proinflammatory proteins without affecting the microglia’s ability to continue clearing the protein buildup related to Alzheimer’s.”
“The nasal spray appears to regulate microglia activity effectively. By preventing overactivation of microglia, it reduces harmful inflammation while allowing these cells to continue clearing beta-amyloid plaques, which are associated with Alzheimer’s progression. This balance is crucial because excessive inflammation can lead to neuron damage while clearing plaques is necessary to maintain brain health.”
However, he warned MNT of potential side effects. “While the study shows promising results, possible side effects need to be evaluated,” he cautioned.
“Adverse reactions could arise from altering immune cell behavior, unexpected impacts on other cell types, or long-term consequences of manipulating the brain’s immune response. Clinical trials would need to monitor any immune-related side effects or unexpected impacts on cognition,” Allder further explained.
Kloske stressed the need for further research to increase the range of Alzheimer’s treatments available.
“Treatments that target Alzheimer’s from all angles and all stages of the disease are essential, and that’s why strategic research funding that works to diversify the therapies in the pipeline is so important,“ she told us.
“It is also important to consider different mechanisms of drug delivery, such as intranasal delivery as is used in this research study. All evidence-based paths to treatment targets and drug delivery methods of Alzheimer’s and all other dementia should be explored,” added Kloske.
“The Alzheimer’s Association envisions a future where there are many treatments available that address these diseases in multiple ways and can be combined into powerful combination therapies, most likely in conjunction with brain-healthy lifestyle guidance,” she told MNT.
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This article originally appeared here and was republished with permission.
