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Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid [CSF]

ABSTRACT: Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid [CSF]

PROVIDER: PRJNA557207 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9854950.fastq.gz	Fastqsanger.gz
	SRR9854951.fastq.gz	Fastqsanger.gz
	SRR9854942.fastq.gz	Fastqsanger.gz
	SRR9854952.fastq.gz	Fastqsanger.gz
	SRR9854943.fastq.gz	Fastqsanger.gz

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Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid [CSF]

Project description:Alzheimer’s disease (AD) is an age-related neurodegenerative disorder in which neuroinflammation plays a critical function. Recurring viral infections and loss of immune competence increase risk for developing AD, yet the cellular and molecular mechanisms driving these immune changes are unknown. Here we performed mass cytometry of peripheral blood mononuclear cells and detected an immunologic signature of AD characterized by increased numbers of CD8+ T effector memory CD45RA+ (TEMRA) cells. CD8+ TEMRA cells were negatively associated with cognition and single cell RNA sequencing revealed their cytotoxic effector function. Strikingly, we discovered identical, shared T cell receptors (TCRs) of clonally expanded CD8+ TEMRA cells in cerebrospinal fluid (CSF) of three AD patients. Deep TCR sequencing, machine learning, and peptide screens identified the HLA-B*08:01-restricted Epstein-Barr virus trans-activator protein BZLF1 as the cognate antigen of a novel AD CSF TCR . These results provide the first evidence of clonal, antigen-specific T cells patrolling the intrathecal space of brains affected by age-related neurodegeneration

2019-11-04 | GSE134577 | GEO

Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid

Project description:Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid

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Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid [TEMRA]

Project description:Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid [TEMRA]

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Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid [TCR-seq]

Project description:Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid [TCR-seq]

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Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid [TEMRA]

2019-11-04 | GSE134576 | GEO

Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid [TCR-seq]

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Peripheral immunomodulatory effects of Apolipoprotein E4 on Alzheimer's disease - Immune Enrichment

Project description:Apolipoprotein E (APOE) is a lipid and cholesterol transport molecule known to influence Alzheimer's disease (AD) risk in an isoform-specific manner. In particular, the APOE E4 allele is the largest genetic risk factor for late-onset sporadic AD. Our recent findings uncovered activated, clonally expanded T cells in AD cerebrospinal fluid (CSF). This T cell phenotype occurred concomitantly with altered expression of APOE in CSF monocytes. Yet, whether APOE variants differentially affect peripheral immunity systems remains unknown. In this study, we performed targeted immune profiling using single-cell epigenetic and transcriptomic analysis of peripheral blood mononuclear cells (PBMC). We analyzed 55 age-matched healthy control (HC) and AD patients with equal distribution of APOE E3/E3, E3/E4, and E4/E4 genotypes. We reveal dysregulation in monocytes and clonally expanded T cells that are distinct to AD patients carrying the APOE E4/E4 genotype. Additionally, we find APOE isoform-dependent chromatin accessibility differences that correspond to RNA expression changes. Cumulatively, these results uncover APOE isoform-dependent changes to peripheral immunity in AD.

2024-03-22 | GSE227991 | GEO

scRNAseq + scV(D)J of cerebrospinal fluid samples across age

Project description:Cerebrospinal fluid (CSF) contains a tightly regulated, specialized immune system. Yet, little is known about how aging influences CSF immunity in cognitively typical versus cognitively impaired individuals. Here, we performed single cell RNA sequencing (scRNAseq) on CSF collected from 45 cognitively typical subjects ranging from 54-82 years old. We then assessed age-related transcriptomic changes using several bioinformatic approaches, including linear and local polynomial regression. We reveal pronounced changes to several CSF immune cell types that occur around age 75, including alterations to clonally expanded T cells and activated monocytes. We then compared CSF immune systems from cognitively typical subjects to 14 subjects with mild cognitive impairment or Alzheimer’s disease. Our results indicate disparate age-related CSF immune system perturbations in cognitively impaired subjects. These results highlight the potential to utilize CSF immune changes to identify age-related neuroinflammation in cognitively impaired individuals.

2022-12-12 | GSE200164 | GEO

Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-11-04 | GSE134578 | GEO

Clonally expanded T cells reveal immunogenicity of rhabdoid tumors

Project description:Clonally expanded T cells reveal immunogenicity of rhabdoid tumors

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