Could a new approach halt or slow down progression?

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New research suggests that targeting a certain protein in the brain could help clear toxic plaques. Image credit: Karen Moskowitz/Getty Images.
  • About 32 million people globally have Alzheimer’s disease.
  • Researchers continue to look for a way to stop or slow disease progression.
  • Researchers from the Icahn School of Medicine at Mount Sinai found that changing certain cellular interactions helps clear out beta-amyloid plaques from the brain, considered a sign of Alzheimer’s disease.
  • Scientists believe these findings may lead to new treatment options for the condition.

Researchers continue to look for a way to stop or slow the progression of Alzheimer’s disease — a type of dementia affecting about 32 million people around the world.

One such team of researchers hails from the Icahn School of Medicine at Mount Sinai in New York. In their new study published in the journal Nature Neuroscience, researchers found that changing certain cellular interactions helps clear out beta-amyloid plaques from the brain, considered a sign of Alzheimer’s disease.

Medical News Today spoke to the three senior authors of the study about its findings: Roland H. Friedel, PhD, who is an associate professor of neuroscience and neurosurgery at Icahn, Hongyan Zou, MD, PhD, a professor of neurosurgery and neuroscience at this institution, and Bin Zhang, PhD, who is professor of genetics and genomic sciences at Icahn.

“Alzheimer’s disease remains a medical challenge as currently effective treatment is still not available,” the study authors pointed out.

“Amyloid plaque is a pathological hallmark of Alzheimer’s disease and plaque burden positively correlates with disease severity. Amyloid plaques are neurotoxic — finding ways to help clear out plaques will help reduce neurotoxicity and attenuate neuroinflammation,” they told us.

For this study, researchers focused on a protein called plexin-B1.

“Plexin-B1 is a membrane receptor, originally identified as an axon guidance (molecule) important for axon wiring during neurodevelopment,” the study authors explained to MNT.

“Recent big data analysis by Dr. Bin Zhang’s system biology group computationally identified plexin-B1 as a hub gene underlying late-onset Alzheimer’s disease,” they told us.

“This project showcases a team approach from three different labs — hence three senior authors — to tackle the function of plexin-B1 in Alzheimer’s disease for the first time,” noted the study authors.

The scientists looked at how plexin-B1 protein interacted with reactive astrocytes — cells in the central nervous system, including the brain, that activate in response to disease or injury.

The senior authors explained that:

“Astrocytes are a type of glial cells that support neuronal function. Reactive astrocytes react to Alzheimer’s disease by surrounding the amyloid plaques, forming a structure called [a] glial net.”

“Our study found that plexin-B1 activation in reactive astrocytes prevents them from [properly functioning] to clear plaques,” they continued. “Removing plexin-B1 can reverse this, leading to better amyloid clearance and smaller plaque burden.”

All three researchers are currently working to find therapeutic ways to target plexin-B1. Zhang’s team is reportedly trying to identify candidate drugs using artificial intelligence (AI)-aided approaches. And Zou and Friedel’s labs are teaming up to generate function-blocking antibodies against plexin-B1.

“The three teams will work together to identify effective drugs or antibodies to modulate plexin-B1 function in reactive astrocytes,” the study authors said. “We believe our research will contribute significantly to the global effort to combat Alzheimer’s disease.”

“This study not only confirms one of the most important predictions from our gene network models but also significantly advances our understanding of Alzheimer’s. It lays a solid foundation for developing novel therapeutics targeting such highly predictive network models,” they argued.

“Our study opens new pathways for Alzheimer’s research, emphasizing the importance of cellular interactions in developing neurodegenerative disease treatments.”

– Roland H. Friedel, PhD; Hongyan Zou, MD, PhD; Bin Zhang, PhD

After reviewing this study, Karen D. Sullivan, PhD, ABPP, a board-certified neuropsychologist, owner of I CARE FOR YOUR BRAIN, and Reid Healthcare Transformation Fellow at FirstHealth of the Carolinas in Pinehurst, NC, who was not involved in the research, told MNT this innovative study offers a new window of hope for Alzheimer’s disease treatment.

“With so many therapeutics focusing on beta-amyloid, this evidence suggests that by relaxing the spacing of the ‘connector cells’, i.e., glia, we may be able to reduce neuroinflammation and help the pathological plaques of Alzheimer’s disease to be more compact,” Sullivan continued. “In turn, this is expected to reduce the number of neurons that get consumed by the disease i.e., less cell death.”

However, the research is still at an early, preclinical stage, she cautioned.

“This study was done in a genetic mouse model of Alzheimer’s disease,” noted Sullivan. “We always want [to] see results like this translate well into the human brain before we get too hopeful that a new drug can be developed from this discovery.”

MNT also spoke with Clifford Segil, DO, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, about this study. Segil was also not involved in this research.

Segil expressed more doubt about the therapeutic potential tied to this study’s findings. In his view, targeting plaque build-up in the brain may not necessarily be the best way to go in fighting Alzheimer’s.

Without mincing words, he said: “It upsets me to see researchers blindly note cognitive decline and memory loss from neurodegeneration are linked to amyloid-beta and neurofibrillary tangles, when clinicians on the front line treating and diagnosing patients with dementias continue to sour on the ‘amyloid hypothesis’ as clinically-available and highly-effective anti-brain-amyloid medications continue to produce modest improvements in cognition per pharmaceutical company provided data and without any noticeable clinical improvements to [a] clinical neurologist.”

Referencing the recent controversy that cast a shadow of doubt over the widely-embraced hypothesis that beta-amyloid plaques are at least partly to brain for Alzheimer’s symptoms, Segil pointed out that:

“This paper’s claim [that] amyloid and tangles cause cognitive decline and memory loss is becoming less believable over time as anti-brain amyloid medications are being used and patients receiving these medications in the real world are not having any noticeable improvements.”

He also noted that many clinicians like himself see patients with high brain-amyloid burden without any cognitive complaints, as well as those with low brain-amyloid burden and disabling and severe cognitive complaints.

“Findings focusing on removing amyloid plaque buildup are not going to help find new ways to treat the memory loss patients with Alzheimer’s dementia get,” Segil claimed.

Nevertheless, he met some of the other study findings with more enthusiasm, saying: “I am excited to see if the plexin-B1 noted in this study that works on brain neuron support cells or glia can produce improvements in memory separate [from] their effects on brain amyloid.”

“I would like more research done on brain microglia and [the] brain lymphatic system,” Segil added. “When I obtained my [Bachelor of Science] in neuroscience in 1996, there was no agreement then [that the] brain had a lymphatic system, and more research should be done on novel ways to engage brain microglial cell function as they relate to memory loss,” he told us.

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