Cancer-Like Metabolic Changes in Alzheimer's Disease Neurons

Unravel cancer-like metabolic changes in Alzheimer’s Disease neurons and their impact on protein modifications and gene splicing to identify new intervention strategies.

This research focuses on how metabolic changes impact gene expression and protein modifications in Alzheimer’s Disease (AD). Using neurons from AD patients, we’ve identified disruptions in metabolic pathways leading to abnormal gene processing. Our study aims to understand how these changes contribute to key AD features, such as tau tangle formation. By understanding upstream metabolic pathways of AD pathology, we aim to identify potential intervention targets to rescue the loss of synaptic function and prevent neuronal cell death.

This project investigates cancer-like metabolic rewiring in Alzheimer’s Disease neurons, focusing on how oncometabolic changes affect gene splicing and the phospho-proteome. The use of directly induced neurons (iNs) from adult human fibroblasts provides a novel model that maintains age-associated and disease-specific neuronal dysfunctions. The combination of single-cell long-read mRNA sequencing, isotope-labeled metabolic flux tracing, and targeted metabolic interventions offers an innovative approach to understanding and potentially alleviating AD-related changes at the metabolic level.

This study could provide crucial insights into the metabolic mechanisms underlying Alzheimer’s Disease, potentially leading to new therapeutic strategies targeting cancer-like metabolic changes in neurons. This research may pave the way for more effective treatments or preventive measures for Alzheimer’s Disease, potentially improving the quality of life for millions of patients and their families. In the research field, this study will advance our understanding of the complex interplay between metabolism and neurodegeneration, opening up new avenues for investigation and drug development.