Biomarkers

Area of Science:

• Neuroscience
• Genetics
• Gerontology

Background:

• Adults with Down syndrome (DS) represent the largest genetically defined group at risk for Alzheimer's disease (AD).
• Lifelong overexpression of the APP gene on chromosome 21 in DS individuals leads to near-universal development of AD neuropathology by mid-adulthood.
• Down syndrome-associated Alzheimer's disease (DSAD) is a prime example of genetically determined AD.

Purpose of the Study:

• To highlight recent advancements in understanding DSAD.
• To showcase DSAD's role as a model for AD research, including early detection, biomarker development, and therapeutic strategies.
• To discuss the implications of DSAD research for broader AD understanding, including APOE4 homozygotes.

Main Methods:

• Large-scale international consortia (e.g., ABC-DS, Horizon21) have advanced the study of DSAD's natural history and biology.
• Inclusion of DSAD in updated Alzheimer's Association diagnostic criteria.
• Leveraging population-based studies, fluid biomarkers, and imaging techniques.

Main Results:

• Significant progress in understanding the natural history and biology of DSAD.
• DSAD is now recognized and included in new diagnostic criteria for AD.
• Insights from DSAD are influencing the reconceptualization of other genetically determined AD forms, like APOE4 homozygotes.

Conclusions:

• DSAD research has entered a new era with increased funding and scientific focus.
• DSAD serves as a critical model for developing early detection methods, biomarkers, and disease-modifying treatments for AD.
• Clinical trials in DSAD mark a significant step towards AD prevention and treatment for high-risk populations.