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pmid:37866940

[Identification of Peripheral Blood GZMK + CD8 + T Cells As Biomarkers of Alzheimer's Disease Based on Single-Cell Transcriptome].

Tingting Duan · Jinyu Chu · Feifei Hu

Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023 doi:10.12182/20230960107

Paper

complete

Experiment

complete

Data

partial

Analysis

absent

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:37866940
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science-record
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title
[Identification of Peripheral Blood GZMK + CD8 + T Cells As Biomarkers of Alzheimer's Disease Based on Single-Cell Transcriptome].
doi
10.12182/20230960107
pmid
37866940
authors array · 3 items
[0]
Tingting Duan
[1]
Jinyu Chu
[2]
Feifei Hu
journal
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition
year
2023
abstract
Objective: Based on single-cell RNA sequencing (scRNA-seq) to explore immune characteristics in the peripheral blood of patients with Alzheimer's disease (AD) as biomarkers. Methods: GSE168522, the scRNA-seq dataset of AD peripheral blood immune cells, was downloaded from the Gene Expression Omnibus (GEO) database and was analyzed in the RAD-Blood web server (http://www.bioinform.cn/RAD-Blood/). The changes in blood cell composition in AD patients were analyzed. The abnormal communications between different types of cells in AD patients were investigated by the CellChat R package. Results: There were two kinds of CD8 + T cells in the blood of AD patients and healthy individuals, one of which highly expressed granzyme K ( GZMK) (false discovery rate [FDR]<0.05), and the other highly expressed GZMA, GZMB, and GZMH (FDR<0.05). In the blood of AD patients, the content of GZMK + CD8 + T cells was increased by 32.9% ( P=5.15E-21), their interactions with other cell types were increased, and they might be associated with AD through the abnormal signal transduction of major histocompatibility complex class Ⅰ (MHC-Ⅰ). Erythrocyte provided the main ligands, that are, human leukocyte antigen (HLA) class Ⅰ molecules, including HLA- A, HLA- B, HLA- C, and HLA- E, for the abnormal MHC-Ⅰ signaling pathway of GZMK + CD8 + T cells. The RESISTIN signaling pathway was specifically enriched in the blood of AD patients. Conclusion: The increased content of peripheral blood GZMK + CD8 + T cells, the increased interaction between GZMK + CD8 + T cells and erythrocytes, and the enhanced RESISTIN pathway are potential blood biomarkers of AD.
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外周血单细胞转录组数据来源于GEO数据库的GSE168522[6]数据集,该数据集提取并纯化了4例(GSM5145403、GSM5145404、GSM5145405和GSM5145406)AD患者和2名(GSM5145401和GSM5145402)正常人的外周血单核细胞,并使用10× Genomics Chromium测序平台进行scRNA-seq。
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methodological
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外周血单细胞转录组数据来源于GEO数据库的GSE168522[6]数据集,该数据集提取并纯化了4例(GSM5145403、GSM5145404、GSM5145405和GSM5145406)AD患者和2名(GSM5145401和GSM5145402)正常人的外周血单核细胞,并使用10× Genomics Chromium测序平台进行scRNA-seq。
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GZMK+ CD8+ T细胞在AD患者血液中含量升高32.9%(P=5.15E-21),与其他细胞类型的交互作用增加,并可能通过主要组织相容性复合体Ⅰ类(major histocompatibility complex class Ⅰ, MHC-Ⅰ)信号转导异常与AD关联,红细胞为GZMK+ CD8+ T细胞MHC-Ⅰ信号通路异常提供了主要配体,即人类白细胞抗原(human leukocyte antigen, HLA)Ⅰ类分子(HLA-A、HLA-B、HLA-C和HLA-E)。
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GZMK+ CD8+ T细胞在AD患者血液中含量升高32.9%(P=5.15E-21),与其他细胞类型的交互作用增加,并可能通过主要组织相容性复合体Ⅰ类(major histocompatibility complex class Ⅰ, MHC-Ⅰ)信号转导异常与AD关联,红细胞为GZMK+ CD8+ T细胞MHC-Ⅰ信号通路异常提供了主要配体,即人类白细胞抗原(human leukocyte antigen, HLA)Ⅰ类分子(HLA-A、HLA-B、HLA-C和HLA-E)。
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sections[0] "Abstract" paragraph 3
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GZMK+ CD8+ T细胞在AD患者血液中含量升高32.9%(P=5.15E-21),与其他细胞类型的交互作用增加,并可能通过主要组织相容性复合体Ⅰ类(major histocompatibility complex class Ⅰ, MHC-Ⅰ)信号转导异常与AD关联,红细胞为GZMK+ CD8+ T细胞MHC-Ⅰ信号通路异常提供了主要配体,即人类白细胞抗原(human leukocyte antigen, HLA)Ⅰ类分子(HLA-A、HLA-B、HLA-C和HLA-E)。
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GZMK+ CD8+ T细胞在AD患者血液中含量升高32.9%(P=5.15E-21),与其他细胞类型的交互作用增加,并可能通过主要组织相容性复合体Ⅰ类(major histocompatibility complex class Ⅰ, MHC-Ⅰ)信号转导异常与AD关联,红细胞为GZMK+ CD8+ T细胞MHC-Ⅰ信号通路异常提供了主要配体,即人类白细胞抗原(human leukocyte antigen, HLA)Ⅰ类分子(HLA-A、HLA-B、HLA-C和HLA-E)。
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外周血单细胞转录组数据来源于GEO数据库的GSE168522[6]数据集,该数据集提取并纯化了4例(GSM5145403、GSM5145404、GSM5145405和GSM5145406)AD患者和2名(GSM5145401和GSM5145402)正常人的外周血单核细胞,并使用10× Genomics Chromium测序平台进行scRNA-seq。
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外周血单细胞转录组数据来源于GEO数据库的GSE168522[6]数据集,该数据集提取并纯化了4例(GSM5145403、GSM5145404、GSM5145405和GSM5145406)AD患者和2名(GSM5145401和GSM5145402)正常人的外周血单核细胞,并使用10× Genomics Chromium测序平台进行scRNA-seq。
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Single-cell RNA sequencing reveals B cells-related molecular biomarkers for Alzheimer's Disease
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外周血单细胞转录组数据来源于GEO数据库的GSE168522[6]数据集,该数据集提取并纯化了4例(GSM5145403、GSM5145404、GSM5145405和GSM5145406)AD患者和2名(GSM5145401和GSM5145402)正常人的外周血单核细胞,并使用10× Genomics Chromium测序平台进行scRNA-seq。
basis
The paper names GSE168522 in GEO(Gene Expression Omnibus)数据库 and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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of Alzheimer's Disease Based on Single-Cell Transcriptome].
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Objective: Based on single-cell RNA sequencing (scRNA-seq) to explore immune characteristic
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ective: Based on single-cell RNA sequencing (scRNA-seq) to explore immune characteristics in the pe
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(AD) as biomarkers. Methods: GSE168522, the scRNA-seq dataset of AD peripheral blood immune cells,
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37866940", "kind": "science-record", "revision": 1, "content_hash": "sha256:da811b681d050118b0b1bffb0e2689a674706493ec0a31f9903f968153d80372", "created_at": "2026-11-01T19:02:43Z", "updated_at": "2026-11-01T19:02:43Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "[Identification of Peripheral Blood GZMK + CD8 + T Cells As Biomarkers of Alzheimer's Disease Based on Single-Cell Transcriptome].", "doi": "10.12182/20230960107", "pmid": "37866940", "authors": ["Tingting Duan", "Jinyu Chu", "Feifei Hu"], "journal": "Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition", "year": 2023, "abstract": "Objective: Based on single-cell RNA sequencing (scRNA-seq) to explore immune characteristics in the peripheral blood of patients with Alzheimer's disease (AD) as biomarkers.\nMethods: GSE168522, the scRNA-seq dataset of AD peripheral blood immune cells, was downloaded from the Gene Expression Omnibus (GEO) database and was analyzed in the RAD-Blood web server (http://www.bioinform.cn/RAD-Blood/). The changes in blood cell composition in AD patients were analyzed. The abnormal communications between different types of cells in AD patients were investigated by the CellChat R package.\nResults: There were two kinds of CD8 + T cells in the blood of AD patients and healthy individuals, one of which highly expressed granzyme K ( GZMK) (false discovery rate [FDR]<0.05), and the other highly expressed GZMA, GZMB, and GZMH (FDR<0.05). In the blood of AD patients, the content of GZMK + CD8 + T cells was increased by 32.9% ( P=5.15E-21), their interactions with other cell types were increased, and they might be associated with AD through the abnormal signal transduction of major histocompatibility complex class Ⅰ (MHC-Ⅰ). Erythrocyte provided the main ligands, that are, human leukocyte antigen (HLA) class Ⅰ molecules, including HLA- A, HLA- B, HLA- C, and HLA- E, for the abnormal MHC-Ⅰ signaling pathway of GZMK + CD8 + T cells. The RESISTIN signaling pathway was specifically enriched in the blood of AD patients.\nConclusion: The increased content of peripheral blood GZMK + CD8 + T cells, the increased interaction between GZMK + CD8 + T cells and erythrocytes, and the enhanced RESISTIN pathway are potential blood biomarkers of AD.", "claims": [{"id": "claim-data-access", "statement": "外周血单细胞转录组数据来源于GEO数据库的GSE168522[6]数据集,该数据集提取并纯化了4例(GSM5145403、GSM5145404、GSM5145405和GSM5145406)AD患者和2名(GSM5145401和GSM5145402)正常人的外周血单核细胞,并使用10× Genomics Chromium测序平台进行scRNA-seq。", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37866940", "locator": "sections[5] \"数据收集\" paragraph 2", "quote": "外周血单细胞转录组数据来源于GEO数据库的GSE168522[6]数据集,该数据集提取并纯化了4例(GSM5145403、GSM5145404、GSM5145405和GSM5145406)AD患者和2名(GSM5145401和GSM5145402)正常人的外周血单核细胞,并使用10× Genomics Chromium测序平台进行scRNA-seq。"}], "state": "complete"}, {"id": "claim-target-result", "statement": "GZMK+ CD8+ T细胞在AD患者血液中含量升高32.9%(P=5.15E-21),与其他细胞类型的交互作用增加,并可能通过主要组织相容性复合体Ⅰ类(major histocompatibility complex class Ⅰ, MHC-Ⅰ)信号转导异常与AD关联,红细胞为GZMK+ CD8+ T细胞MHC-Ⅰ信号通路异常提供了主要配体,即人类白细胞抗原(human leukocyte antigen, HLA)Ⅰ类分子(HLA-A、HLA-B、HLA-C和HLA-E)。", "kind": "quantitative", "target": {"value": 32.9, "unit": "per cent", "tolerance": null, "source": "GZMK+ CD8+ T细胞在AD患者血液中含量升高32.9%(P=5.15E-21),与其他细胞类型的交互作用增加,并可能通过主要组织相容性复合体Ⅰ类(major histocompatibility complex class Ⅰ, MHC-Ⅰ)信号转导异常与AD关联,红细胞为GZMK+ CD8+ T细胞MHC-Ⅰ信号通路异常提供了主要配体,即人类白细胞抗原(human leukocyte antigen, HLA)Ⅰ类分子(HLA-A、HLA-B、HLA-C和HLA-E)。"}, "evidence": [{"asset": "source:pmid:37866940", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "GZMK+ CD8+ T细胞在AD患者血液中含量升高32.9%(P=5.15E-21),与其他细胞类型的交互作用增加,并可能通过主要组织相容性复合体Ⅰ类(major histocompatibility complex class Ⅰ, MHC-Ⅰ)信号转导异常与AD关联,红细胞为GZMK+ CD8+ T细胞MHC-Ⅰ信号通路异常提供了主要配体,即人类白细胞抗原(human leukocyte antigen, HLA)Ⅰ类分子(HLA-A、HLA-B、HLA-C和HLA-E)。"}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "GZMK+ CD8+ T细胞在AD患者血液中含量升高32.9%(P=5.15E-21),与其他细胞类型的交互作用增加,并可能通过主要组织相容性复合体Ⅰ类(major histocompatibility complex class Ⅰ, MHC-Ⅰ)信号转导异常与AD关联,红细胞为GZMK+ CD8+ T细胞MHC-Ⅰ信号通路异常提供了主要配体,即人类白细胞抗原(human leukocyte antigen, HLA)Ⅰ类分子(HLA-A、HLA-B、HLA-C和HLA-E)。", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37866940"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE168522"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE168522"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37866940", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.12182/20230960107", "sha256": "sha256:bb2b77d2857995639b3f9b91168a83416ad0b41589fe9acd8f87d5bfee9991e5", "bytes": 17252, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.12182/20230960107", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10579064", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE168522", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE168522", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE168522", "version": null, "note": "外周血单细胞转录组数据来源于GEO数据库的GSE168522[6]数据集,该数据集提取并纯化了4例(GSM5145403、GSM5145404、GSM5145405和GSM5145406)AD患者和2名(GSM5145401和GSM5145402)正常人的外周血单核细胞,并使用10× Genomics Chromium测序平台进行scRNA-seq。", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "外周血单细胞转录组数据来源于GEO数据库的GSE168522[6]数据集,该数据集提取并纯化了4例(GSM5145403、GSM5145404、GSM5145405和GSM5145406)AD患者和2名(GSM5145401和GSM5145402)正常人的外周血单核细胞,并使用10× Genomics Chromium测序平台进行scRNA-seq。", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM5145401", "GSM5145402", "GSM5145403", "GSM5145404", "GSM5145405", "GSM5145406"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "11154", "taxon": "Homo sapiens", "title": "Single-cell RNA sequencing reveals B cells-related molecular biomarkers for Alzheimer's Disease", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE168522 not downloaded", "asset:data:geo:GSE168522 licence not read"]}, "analysis": {"state": "absent", "methods": [], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": null, "expected_value": 32.9, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}, {"id": "target-published-estimate-p-value", "claim_id": "claim-target-result", "operation": null, "expected_value": 5.0, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": ["method", "operations"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "blocked", "tier": "R4", "blocking_axis": "method", "blocked_on": "method:not_determinable", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (not named), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE168522"], "resolved_accessions": ["GSE168522"], "statements": ["外周血单细胞转录组数据来源于GEO数据库的GSE168522[6]数据集,该数据集提取并纯化了4例(GSM5145403、GSM5145404、GSM5145405和GSM5145406)AD患者和2名(GSM5145401和GSM5145402)正常人的外周血单核细胞,并使用10× Genomics Chromium测序平台进行scRNA-seq。"], "basis": "The paper names GSE168522 in GEO(Gene Expression Omnibus)数据库 and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:37866940", "data:geo:GSE168522"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE168522"]}, "gaps": ["method:not_determinable"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:56:39Z", "independence": "single_reader"}, "evidence_check": {"method": null, "availability": null}, "calls": 5, "usage": {"prompt_tokens": 9669, "completion_tokens": 1172, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:37866940", "type": "paper", "label": "pmid:37866940"}, {"id": "source:pmid:37866940", "type": "manuscript", "label": "PMID 37866940 full text"}, {"id": "data:geo:GSE168522", "type": "dataset", "label": "GEO GSE168522"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37866940", "type": "paper", "label": "pmid:37866940"}, {"id": "source:pmid:37866940", "type": "manuscript", "label": "PMID 37866940 full text"}, {"id": "data:geo:GSE168522", "type": "dataset", "label": "GEO GSE168522"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37866940", "type": "extraction", "used": ["source:pmid:37866940"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE168522", "type": "accession_resolution", "used": ["data:geo:GSE168522"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": null, "parent_hash": null, "fork_of": null, "generation": 0}, "gaps": ["asset:data:geo:GSE168522 licence not read", "asset:data:geo:GSE168522 not downloaded", "execution.not_run", "method", "operations", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["of Alzheimer's Disease Based on Single-Cell Transcriptome].", "Objective: Based on single-cell RNA sequencing (scRNA-seq) to explore immune characteristic"], "order_basis": "paper_text_order:71", "id": "assay:1"}, {"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Objective: Based on single-cell RNA sequencing (scRNA-seq) to explore immune characteristic", "ective: Based on single-cell RNA sequencing (scRNA-seq) to explore immune characteristics in the pe", "(AD) as biomarkers. Methods: GSE168522, the scRNA-seq dataset of AD peripheral blood immune cells,"], "order_basis": "paper_text_order:131", "id": "assay:2"}]}