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Recapitulation of pathophysiological features of AD in SARS-CoV-2 infected subjects

ABSTRACT: Recapitulation of pathophysiological features of AD in SARS-CoV-2 infected subjects

PROVIDER: PRJNA991578 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25152616_1.fastq.gz	Fastqsanger.gz
	SRR25152616_2.fastq.gz	Fastqsanger.gz
	SRR25152617_1.fastq.gz	Fastqsanger.gz
	SRR25152617_2.fastq.gz	Fastqsanger.gz
	SRR25152618_1.fastq.gz	Fastqsanger.gz

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Recapitulation of pathophysiological features of AD in SARS-CoV-2 infected subjects

Project description:Infection with the etiological agent of COVID-19, SARS-CoV-2, appears capable of impacting cognition, which some patients with Post-acute Sequelae of SARS-CoV-2 (PASC). To evaluate neuro-pathophysiological consequences of SARS-CoV-2 infection, we examine transcriptional and cellular signatures in the Broadman area 9 (BA9) of the frontal cortex and the hippocampal formation (HF) in SARS-CoV-2, Alzheimer’s disease (AD) and SARS-CoV-2 infected AD individuals, compared to age- and gender-matched neurological cases. Here we show similar alterations of neuroinflammation and blood-brain barrier integrity in SARS-CoV-2, AD, and SARS-CoV-2 infected AD individuals. Distribution of microglial changes reflected by the increase of Iba-1 reveal nodular morphological alterations in SARS-CoV-2 infected AD individuals. Similarly, HIF-1α is significantly upregulated in the context of SARS-CoV-2 infection in the same brain regions regardless of AD status. The finding may help to inform decision-making regarding therapeutic treatments in patients with neuro-PASC, especially those at increased risk of developing AD.

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Project description:Brain organoids (BO) enabled the investigation of human corticogenesis in-vitro with an increasing range of protocols achieving its remarkable recapitulation. However, we lack a resource gathering fetal cortex-specific gene co-expression patterns and their behavior in BO. We complement the current knowledge with a benchmarking of BO versus human corticogenesis, integrating: transcriptomes from in-house differentiated cortical BO (CBO), in-house processed human fetal brain samples, analysis of transcriptomes from different BO systems and of pre-natal cortical samples from the BrainSpan Atlas.

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