Redefining the Alzheimer's Timeline: Tracing Its Origin to Embryogenesis

Older population is primarily affected by Alzheimer's disease, but a study discovered indications of the disease in cell culture models simulating its early onset.

While Alzheimers disease (AD) predominantly impacts the older population, recent research indicates that early signs of the disease can be observed in cell culture models of early human brain development, suggesting that its origins may occur much earlier in life, potentially during embryogenesis ().

Alzheimer’s disease is a highly prevalent, debilitating, and potentially fatal neurodegenerative disease with limited treatment options.

Unveiling the Hidden Origins

Patients are typically diagnosed at an advanced disease stage, limiting the possibilities for early therapeutic intervention. Although for most patients the disease cause is unknown and likely multifactorial, some patients have known mutations in genes affecting neuronal function and survival, leading to familial forms of AD.

Risk Factors for Alzheimers Disease
Cognitively normal adults exhibiting atrophy of their temporal lobe or damage to blood vessels in the brain are more likely to develop Alzheimer’s disease.

‘Although Alzheimer's disease (AD) predominantly targets older individuals, emerging research has identified early disease markers in cell culture models that mimic the early stages of human brain development, pointing to the possibility that the disease may originate during embryogenesis, reshaping our understanding of its timeline. # Alzheimer's Disease, # Life Origins, # Embryogenesis ’

Abnormal brain structures have been seen in children and young adults with familial AD years before the onset of AD symptoms, suggesting that the disease may have its origins much earlier in life.

Jenny Hsieh and colleagues from the University of Texas at San Antonio, USA now asked how AD-associated gene mutations affect early human brain development. The researchers grew so-called cortical spheres, which are small clumps of cells resembling human embryonic brains, from CRISPR-edited stem cell lines harboring fAD mutations.

Discovering Clues in Cell Culture Models

Intriguingly, AD mutations interfered with the normal development of these cortical spheres, whereby mutant spheres were larger and contained less mature and functioning neurons compared to cortical spheres without the mutations.

By pinpointing the underlying molecular pathways, the researchers could identify points of intervention to restore normal brain development in their cortical sphere model.

Sexuality Among People With Dementia and Other Cognitive Problems
Women with lower cognitive scores were less likely than men with lower cognitive scores to have intimate partners, found study.

Interestingly different types of AD-associated mutations caused distinct developmental abnormalities in the cortical spheres, highlighting the need for tailoring therapies individually for each patient.

This work, published in the recent issue of Stem Cell Reports, paves the way for studying AD in its early stages with the possibility of identifying more effective or preventive treatments for AD in a patient-specific fashion.

New Genes That may Contribute to Alzheimer's Disease Discovered
The newly discovered genes may suggest an inflammatory response and changes in the protein production contribute to the overall neurodegeneration witnessed in AD.

Reference:

Familial Alzheimer’s disease-associated PSEN1 mutations affect neurodevelopment through increased Notch signaling - (https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(23)00197-2?)

Source-Eurekalert