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. 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.
Alzheimer’s disease remains a medical challenge as currently effective treatment is still not available. 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.
Plexin-B1 is a membrane receptor, originally identified as an axon guidance (molecule) important for axon wiring during neurodevelopment. 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. 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. The scientists looked at how plexin-B1 protein interacted with reactive astrocyte cells in the central nervous system, including the brain, that activate in response to disease or injury.
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.
With so many therapeutics focusing on beta-amyloid, this evidence suggests that by relaxing the spacing of the ‘connector cells’, i.e., glia, researchers may be able to reduce neuroinflammation and help the pathological plaques of Alzheimer’s disease to be more compact. 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. 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.
