Pilot Use-Case

CLARA Pilot Use-Case: Evaluating the Calcium Brain Aging and APOE Cascade Hypotheses

The CLARA pilot use-case focuses on understanding the complex interactions between apolipoprotein E (APOE) and lipids in the brain, and their impact on neuronal health and Alzheimer's disease (AD) progression. This groundbreaking research leverages CLARA's unique interdisciplinary expertise and advanced computing infrastructure to address key challenges in neurodegenerative disease research.

Key Aspects of the Pilot Use-Case

• Target Protein: APOE, a crucial protein involved in brain lipid metabolism and transport
• Research Focus: Mechanisms of APOE-lipid interactions and their effects on neuronal health and AD pathology
• Technological Approach: Utilization of CLARA's three research programs (RPs) and the CLARA Testbed supercomputing infrastructure

Main Objectives

1. Elucidate the precise mechanisms underlying APOE-lipid interactions in the brain
2. Assess the impact of these interactions on neuronal health and clinical manifestations of AD
3. Develop precision medicine tools for predicting disease progression based on APOE-lipid profiles
4. Design and test small molecules to mitigate the negative effects of the APOE4 variant

Potential Breakthroughs

• Enhanced understanding of lipid metabolism's role in neurodegenerative diseases
• Novel biomarkers for early AD detection and progression monitoring
• Personalized treatment strategies based on individual APOE-lipid profiles
• New therapeutic targets for AD intervention

By combining expertise from molecular dynamics, AI-driven data analysis, and multiscale modeling, CLARA aims to make significant advancements in our understanding of AD pathogenesis and pave the way for innovative diagnostic and therapeutic approaches.