Brain transcriptomic profiling reveals common alterations across neurodegenerative and psychiatric disorders

Neurodegenerative and neuropsychiatric disorders (ND-NPs) are multifactorial, polygenic and complex behavioral phenotypes caused by brain abnormalities. Large-scale collaborative efforts have tried to identify the genetic architecture of these conditions. However, the specific and shared underlying...

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Detalles Bibliográficos
Autores: Sadeghi, Iman, Gispert, Juan Domingo, Palumbo, Emilio, Muñoz-Aguirre, Manuel, Wucher, Valentin, D'Argenio, Valeria, Santpere Baró, Gabriel, 1981-, Navarro, Arcadi, Guigó Serra, Roderic, Vilor Tejedor, Natàlia, 1988-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/54541
Acceso en línea:http://hdl.handle.net/10230/54541
http://dx.doi.org/10.1016/j.csbj.2022.08.037
Access Level:acceso abierto
Palabra clave:Brain cell types
Network analysis
Neurodegeneration
Psychiatric disorder
RNA-Seq
Transcriptome profiling
Descripción
Sumario:Neurodegenerative and neuropsychiatric disorders (ND-NPs) are multifactorial, polygenic and complex behavioral phenotypes caused by brain abnormalities. Large-scale collaborative efforts have tried to identify the genetic architecture of these conditions. However, the specific and shared underlying molecular pathobiology of brain illnesses is not clear. Here, we examine transcriptome-wide characterization of eight conditions, using a total of 2,633 post-mortem brain samples from patients with Alzheimer's disease (AD), Parkinson's disease (PD), Progressive Supranuclear Palsy (PSP), Pathological Aging (PA), Autism Spectrum Disorder (ASD), Schizophrenia (Scz), Major Depressive Disorder (MDD), and Bipolar Disorder (BP)-in comparison with 2,078 brain samples from matched control subjects. Similar transcriptome alterations were observed between NDs and NPs with the top correlations obtained between Scz-BP, ASD-PD, AD-PD, and Scz-ASD. Region-specific comparisons also revealed shared transcriptome alterations in frontal and temporal lobes across NPs and NDs. Co-expression network analysis identified coordinated dysregulations of cell-type-specific modules across NDs and NPs. This study provides a transcriptomic framework to understand the molecular alterations of NPs and NDs through their shared- and specific gene expression in the brain.