Human 3D cortical spheroid with a PSEN1 mutation.
Newswise — Alzheimer's disease (AD) primarily impacts the elderly population. However, recent studies have discovered preliminary indications of the disease in cell culture models representing early human brain development. This finding suggests the potential origins of Alzheimer's may occur much earlier in life, potentially during embryogenesis, which is the process of embryo formation and development.
Alzheimer's disease is a widespread and debilitating neurodegenerative condition that can be fatal, and currently, there are limited treatment options available. Diagnosis often occurs when the disease has already progressed significantly, leaving little room for early therapeutic intervention. While the exact cause of the disease is generally unknown and likely involves multiple factors, some patients carry specific genetic mutations that impact neuronal function and survival, leading to familial forms of Alzheimer's.
Remarkably, abnormal brain structures have been observed in individuals, including children and young adults, with familial Alzheimer's long before the onset of symptoms. This suggests that the origins of the disease may trace back to much earlier stages of life. To investigate how Alzheimer's-related gene mutations affect early human brain development, Jenny Hsieh and her colleagues from the University of Texas at San Antonio conducted a study. They utilized CRISPR-edited stem cell lines harboring familial Alzheimer's disease (fAD) mutations and grew "cortical spheres," which are clusters of cells resembling developing human embryonic brains.
The researchers made an intriguing discovery: the AD mutations disrupted the normal development of these cortical spheres. The mutant spheres exhibited larger sizes and contained fewer mature and functional neurons compared to spheres without the mutations. By delving into the molecular pathways involved, the team was able to pinpoint potential targets for intervention that could restore normal brain development in their cortical sphere model. Notably, different types of AD-associated mutations resulted in distinct developmental abnormalities within the cortical spheres, highlighting the importance of tailoring therapies to each individual patient.
This groundbreaking work, published in Stem Cell Reports, opens up new avenues for studying Alzheimer's disease in its early stages. It offers the potential to identify more effective or preventive treatments for Alzheimer's in a patient-specific manner. The findings also underscore the significance of personalized approaches in tackling this complex disease.
RSS