Spatial and single-nucleus transcriptomic analysis of genetic and sporadic forms of Alzheimer's Disease.
bioRxiv
; 2023 Jul 26.
Article
em En
| MEDLINE
| ID: mdl-37546983
The pathogenesis of Alzheimer's disease (AD) depends on environmental and heritable factors, with remarkable differences evident between individuals at the molecular level. Here we present a transcriptomic survey of AD using spatial transcriptomics (ST) and single-nucleus RNA-seq in cortical samples from early-stage AD, late-stage AD, and AD in Down Syndrome (AD in DS) donors. Studying AD in DS provides an opportunity to enhance our understanding of the AD transcriptome, potentially bridging the gap between genetic mouse models and sporadic AD. Our analysis revealed spatial and cell-type specific changes in disease, with broad similarities in these changes between sAD and AD in DS. We performed additional ST experiments in a disease timecourse of 5xFAD and wildtype mice to facilitate cross-species comparisons. Finally, amyloid plaque and fibril imaging in the same tissue samples used for ST enabled us to directly link changes in gene expression with accumulation and spread of pathology.
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Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article