Selective Neuronal Vulnerability in Alzheimer's Disease: A Network-Based Analysis.
Neuron
; 107(5): 821-835.e12, 2020 09 09.
Article
em En
| MEDLINE
| ID: mdl-32603655
ABSTRACT
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 Aß, aging, and neurodegeneration within the most vulnerable neurons in AD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Perfilação da Expressão Gênica
/
Doença de Alzheimer
/
Transcriptoma
/
Aprendizado de Máquina
/
Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Neuron
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2020
Tipo de documento:
Article