| First Author | Roussarie JP | Year | 2020 |
| Journal | Neuron | Volume | 107 |
| Issue | 5 | Pages | 821-835.e12 |
| PubMed ID | 32603655 | Mgi Jnum | J:301432 |
| Mgi Id | MGI:6503448 | Doi | 10.1016/j.neuron.2020.06.010 |
| Citation | Roussarie JP, et al. (2020) Selective Neuronal Vulnerability in Alzheimer's Disease: A Network-Based Analysis. Neuron 107(5):821-835.e12 |
| abstractText | A major obstacle to treating Alzheimer's disease (AD) is our lack of understanding of the molecular mechanisms underlying selective neuronal vulnerability, a key characteristic of the disease. Here, we present a framework integrating high-quality neuron-type-specific molecular profiles across the lifetime of the healthy mouse, which we generated using bacTRAP, with postmortem human functional genomics and quantitative genetics data. We demonstrate human-mouse conservation of cellular taxonomy at the molecular level for neurons vulnerable and resistant in AD, identify specific genes and pathways associated with AD neuropathology, and pinpoint a specific functional gene module underlying selective vulnerability, enriched in processes associated with axonal remodeling, and affected by amyloid accumulation and aging. We have made all cell-type-specific profiles and functional networks available at http://alz.princeton.edu. Overall, our study provides a molecular framework for understanding the complex interplay between Abeta, aging, and neurodegeneration within the most vulnerable neurons in AD. |
