Researchers at Brigham and Women’s Hospital have identified a possible new strategy for treating Alzheimer’s Disease (AD), focused on the role of the SORL1 gene.
The study, published in Cell Reports, may offer a new avenue for personalized neurology treatment for AD patients, especially those unresponsive to existing therapies.
Role of SORL1 in Alzheimer’s
Previous studies have typically focused on three primary genetic drivers of AD (APP, PSEN1, and PSEN2). These genes have been significantly linked to hereditary, early-onset AD.
This study, however, leveraged stem cells from AD patients to examine the SORL1 gene, which is associated with both early and late-onset AD.
Researchers used CRISPR technologies to remove the SORL1 gene from progenitor stem cells from two Alzheimer’s research cohorts.
When these stem cells were programmed to differentiate into different types of brain cells, the loss of SORL1 resulted in a significant decrease in two crucial AD proteins: APOE and CLU.
Without these proteins, neurons were unable to properly regulate lipids, leading to lipid droplets that could impair neuron communication.
Clinical Implications
According to Tracy Young-Pearse, Ph.D., the corresponding author, understanding the subtypes of AD could help tailor treatments more specifically.
“This is getting at a precision neurology approach, with which we can better predict which patients may be responsive to Alzheimer’s treatment strategies that attack specific genes or target the problems they cause.”
Broader Context
Not all patients with AD respond to existing treatments like aducanumab and lecanemab, which focus on reducing amyloid-beta plaques.
Thus, identifying other pathways, like SORL1, can significantly broaden the treatment options and offer more personalized solutions.
Ongoing Work and Future Directions
The researchers plan to explore other pathways related to AD, including those involving microglia, the immune cells in the brain.
They hope to identify additional biological pathways crucial in AD and target them for interventions.
Key Takeaways
This groundbreaking study highlights the importance of a more nuanced approach to treating Alzheimer’s, one that accounts for individual genetic variations.
It opens up new possibilities for targeted therapies, marking a significant step toward personalized treatments for AD.
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The study was published in Cell Reports.
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