Globally, around 32 million people are impacted by Alzheimer’s disease.
The search for methods to halt or decelerate the disease’s development continues.
Mount Sinai’s Icahn School of Medicine researchers discovered that modifying specific cell interactions aids in the elimination of beta-amyloid plaques in the brain, a hallmark of Alzheimer’s disease.
Experts are optimistic that these discoveries could pave the way for novel treatments for the disease.
The quest to discover strategies to cease or slow down Alzheimer’s disease—a form of dementia that affects approximately 32 million individuals worldwide—persists.
A group of researchers from New York’s Icahn School of Medicine at Mount Sinai has contributed to this pursuit. Their latest research, documented in the journal Nature Neuroscience, reveals that alterations in particular cellular interactions can facilitate the removal of beta-amyloid plaques from the brain, a recognized indicator of Alzheimer’s disease.
Medical News Today reached out to the study’s three leading authors for insights: Roland H. Friedel, PhD, an associate professor focused on neuroscience and neurosurgery at Icahn, Hongyan Zou, MD, PhD, a neuroscience and neurosurgery professor at the same institution, and Bin Zhang, PhD, a genetics and genomic sciences professor at Icahn.
“Alzheimer’s disease continues to pose a daunting medical challenge, with efficacious treatments still out of reach,” acknowledged the study’s authors.
They added, “With amyloid plaque being a signature pathology of Alzheimer’s disease, and its abundance closely linked with disease severity, the quest to reduce plaques is crucial. Such reductions have the potential to mitigate neurotoxicity and lessen neuroinflammation.”
Studying a protein’s role in Alzheimer’s progression
In a recent investigation, a research team concentrated on a protein known as plexin-B1.
“Plexin-B1 is identified as a membrane receptor initially, crucial for guiding axons during neurodevelopment,” shared the study’s authors with MNT.
Dr. Bin Zhang’s system biology group, through extensive data analysis, pinpointed plexin-B1 as a critical gene contributing to late-onset Alzheimer’s disease, as the authors relayed.
This initiative is a combined effort from three distinct laboratories, thus attributing to the trio of senior authors. Their collective work delves into the role plexin-B1 plays in Alzheimer’s disease, a topic not previously explored, the authors remarked.
Removing plexin-B1 could facilitate the removal of amyloid plaque
The research team examined interactions between the plexin-B1 protein and reactive astrocytes, which are central nervous system cells that become activated in reaction to disease or injury.
The senior authors detailed that astrocytes are a form of glial cells supporting neuronal functions. In the context of Alzheimer’s disease, reactive astrocytes tend to enclose amyloid plaques, constituting a glial net.
Their findings suggest that when plexin-B1 is activated in these reactive astrocytes, it hinders their ability to effectively clear out amyloid plaques. By removing plexin-B1, there’s potential for enhanced amyloid clearance and subsequently a reduction in plaque burden, they added.
Finding new ways to target plexin-B1
The trio of researchers is currently engaged in developing therapeutic strategies to target plexin-B1. Zhang’s team is utilizing artificial intelligence to scout for potential drugs. Meanwhile, Zou’s and Friedel’s laboratories are collaborating to create antibodies that can block plexin-B1’s function.
Through their joint efforts, the teams aim to pinpoint efficacious drugs or antibodies that can adjust plexin-B1’s activity in reactive astrocytes. “Our collective research endeavors are poised to make a substantial impact in the global fight against Alzheimer’s disease,” the study authors stated.
They further contend, “This investigation not only validates one of the pivotal hypotheses from our gene network models but also markedly enhances our grasp of Alzheimer’s pathology. It establishes a robust base to forge ahead with the creation of innovative treatments directed at such predictive network models.”
Hope for new approaches in Alzheimer’s therapy
In light of this study, Dr. Karen D. Sullivan, PhD, ABPP, a board-certified neuropsychologist and owner of I CARE FOR YOUR BRAIN, who was not involved in the research, shared with MNT her optimism about the potential implications for Alzheimer’s disease treatment.
“This cutting-edge study opens up exciting possibilities for treating Alzheimer’s,” Sullivan remarked. “The findings suggest that by modifying the interplay between ‘connector cells’, namely glia, there could be a reduction in neuroinflammation and a compaction of Alzheimer’s pathological plaques,” she elaborated. This could mean that fewer neurons are engulfed by the disease, i.e., a decrease in neuronal death.
Sullivan advised caution, as this research is still in its nascent, preclinical phase.
“The research was conducted using a genetic mouse model designed to mimic Alzheimer’s disease,” Sullivan pointed out. “We should await positive translation of these findings to the human brain before becoming overly enthusiastic about the possibility of a new medication emerging from this breakthrough.”
Is focusing on removing amyloid plaque buildup the way to go?
Medical News Today also discussed the study with Clifford Segil, DO, a neurologist from Providence Saint John’s Health Center in Santa Monica, CA, who was not part of this research. Segil offered a skeptical perspective regarding the therapeutic promise based on targeting brain plaque accumulation.
He criticized the prevalent hypothesis linking cognitive decline and plaque buildup: “The continuing push to connect cognitive impairment and memory loss solely with amyloid-beta and neurofibrillary tangles is frustrating, especially when front-line clinicians are becoming increasingly disillusioned with the ‘amyloid hypothesis’. This is particularly so as we witness anti-amyloid drugs, though theoretically effective, deliver only minimal cognitive benefits according to pharmaceutical data, without tangible clinical improvements for practicing neurologists.”
Segil referenced controversies casting doubt on the theory that beta-amyloid plaques significantly contribute to Alzheimer’s symptoms. He questioned the paper’s assertion about the causative role of amyloid and tangles in cognitive decline, especially as treatments targeting brain amyloid haven’t yielded noticeable improvements in real-world applications.
He observed the inconsistency between the presence of brain amyloid and cognitive state, noting that some patients with high amyloid levels have no cognitive complaints, while others with low levels face severe cognitive challenges.
Segil dismissed the relevance of amyloid plaque targeting in memory loss treatment for Alzheimer’s, yet he expressed interest in other aspects of the study: “The mention of plexin-B1 is intriguing—if it affects the brain’s neuron-supporting cells, or glia, it could possibly lead to memory improvements independent of amyloid impact.”
He called for more inquiry into brain microglia and the brain’s lymphatic system, noting the evolving scientific consensus since his neuroscience studies in the 1990s. “Back then, there was no consensus on whether the brain had a lymphatic system. Exploring novel ways to stimulate brain microglial cell function in relation to memory loss deserves more attention,” he stated.
