Identification of potential blood biomarkers for early diagnosis of Alzheimer’s disease through immune landscape analysis

Mild cognitive impairment (MCI) is a clinical precursor of Alzheimer’s disease (AD). Recent genetic studies have reported on associations between AD risk genes and immunity. Here, we obtained samples and data from 317 AD, 432 MCI, and 107 cognitively normal (CN) subjects and investigated immune-cell...

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Published innpj aging Vol. 8; no. 1; p. 15
Main Authors Shigemizu, Daichi, Akiyama, Shintaro, Mitsumori, Risa, Niida, Shumpei, Ozaki, Kouichi
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 04.11.2022
Nature Publishing Group
Subjects
631/378/2611
692/499
692/53
692/699/375/132/1283
Aging
Alzheimer's disease
B-cell receptor
Biomarkers
Biomedical and Life Sciences
Biomedicine
Cell Physiology
Cognitive ability
Diagnosis
Geriatrics/Gerontology
Heavy chains
Human Physiology
Immunoglobulins
Leukocytes (neutrophilic)
Lymphocytes B
Lymphocytes T
Neurodegenerative diseases
Neurosciences
Plasma cells
Prediction models
T cell receptors
Online AccessGet full text
ISSN2731-6068
2731-6068
2056-3973
DOI10.1038/s41514-022-00096-9

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Abstract Mild cognitive impairment (MCI) is a clinical precursor of Alzheimer’s disease (AD). Recent genetic studies have reported on associations between AD risk genes and immunity. Here, we obtained samples and data from 317 AD, 432 MCI, and 107 cognitively normal (CN) subjects and investigated immune-cell type composition and immune clonal diversity of T-cell receptor (TRA, TRB, TRG, and TRD) and B-cell receptor (IGH, IGK, and IGL) repertoires through bulk RNA sequencing. We found the proportions of plasma cells, γδ T cells, neutrophils, and B cells were significantly different and the diversities of IGH, IGK, and TRA were significantly small with AD progression. We then identified a differentially expressed gene, WDR37 , in terms of risk of MCI-to-AD conversion. Our prognosis prediction model using the potential blood-based biomarkers for early AD diagnosis, which combined two immune repertoires (IGK and TRA), WDR37 , and clinical information, successfully classified MCI patients into two groups, low and high, in terms of risk of MCI-to-AD conversion (log-rank test P  = 2.57e-3). It achieved a concordance index of 0.694 in a discovery cohort and of 0.643 in an independent validation cohort. We believe that further investigation, using larger sample sizes, will lead to practical clinical use in the near future.
AbstractList Mild cognitive impairment (MCI) is a clinical precursor of Alzheimer’s disease (AD). Recent genetic studies have reported on associations between AD risk genes and immunity. Here, we obtained samples and data from 317 AD, 432 MCI, and 107 cognitively normal (CN) subjects and investigated immune-cell type composition and immune clonal diversity of T-cell receptor (TRA, TRB, TRG, and TRD) and B-cell receptor (IGH, IGK, and IGL) repertoires through bulk RNA sequencing. We found the proportions of plasma cells, γδ T cells, neutrophils, and B cells were significantly different and the diversities of IGH, IGK, and TRA were significantly small with AD progression. We then identified a differentially expressed gene, WDR37 , in terms of risk of MCI-to-AD conversion. Our prognosis prediction model using the potential blood-based biomarkers for early AD diagnosis, which combined two immune repertoires (IGK and TRA), WDR37 , and clinical information, successfully classified MCI patients into two groups, low and high, in terms of risk of MCI-to-AD conversion (log-rank test P  = 2.57e-3). It achieved a concordance index of 0.694 in a discovery cohort and of 0.643 in an independent validation cohort. We believe that further investigation, using larger sample sizes, will lead to practical clinical use in the near future.
Mild cognitive impairment (MCI) is a clinical precursor of Alzheimer’s disease (AD). Recent genetic studies have reported on associations between AD risk genes and immunity. Here, we obtained samples and data from 317 AD, 432 MCI, and 107 cognitively normal (CN) subjects and investigated immune-cell type composition and immune clonal diversity of T-cell receptor (TRA, TRB, TRG, and TRD) and B-cell receptor (IGH, IGK, and IGL) repertoires through bulk RNA sequencing. We found the proportions of plasma cells, γδ T cells, neutrophils, and B cells were significantly different and the diversities of IGH, IGK, and TRA were significantly small with AD progression. We then identified a differentially expressed gene, WDR37, in terms of risk of MCI-to-AD conversion. Our prognosis prediction model using the potential blood-based biomarkers for early AD diagnosis, which combined two immune repertoires (IGK and TRA), WDR37, and clinical information, successfully classified MCI patients into two groups, low and high, in terms of risk of MCI-to-AD conversion (log-rank test P = 2.57e-3). It achieved a concordance index of 0.694 in a discovery cohort and of 0.643 in an independent validation cohort. We believe that further investigation, using larger sample sizes, will lead to practical clinical use in the near future.
Mild cognitive impairment (MCI) is a clinical precursor of Alzheimer's disease (AD). Recent genetic studies have reported on associations between AD risk genes and immunity. Here, we obtained samples and data from 317 AD, 432 MCI, and 107 cognitively normal (CN) subjects and investigated immune-cell type composition and immune clonal diversity of T-cell receptor (TRA, TRB, TRG, and TRD) and B-cell receptor (IGH, IGK, and IGL) repertoires through bulk RNA sequencing. We found the proportions of plasma cells, γδ T cells, neutrophils, and B cells were significantly different and the diversities of IGH, IGK, and TRA were significantly small with AD progression. We then identified a differentially expressed gene, WDR37, in terms of risk of MCI-to-AD conversion. Our prognosis prediction model using the potential blood-based biomarkers for early AD diagnosis, which combined two immune repertoires (IGK and TRA), WDR37, and clinical information, successfully classified MCI patients into two groups, low and high, in terms of risk of MCI-to-AD conversion (log-rank test P = 2.57e-3). It achieved a concordance index of 0.694 in a discovery cohort and of 0.643 in an independent validation cohort. We believe that further investigation, using larger sample sizes, will lead to practical clinical use in the near future.Mild cognitive impairment (MCI) is a clinical precursor of Alzheimer's disease (AD). Recent genetic studies have reported on associations between AD risk genes and immunity. Here, we obtained samples and data from 317 AD, 432 MCI, and 107 cognitively normal (CN) subjects and investigated immune-cell type composition and immune clonal diversity of T-cell receptor (TRA, TRB, TRG, and TRD) and B-cell receptor (IGH, IGK, and IGL) repertoires through bulk RNA sequencing. We found the proportions of plasma cells, γδ T cells, neutrophils, and B cells were significantly different and the diversities of IGH, IGK, and TRA were significantly small with AD progression. We then identified a differentially expressed gene, WDR37, in terms of risk of MCI-to-AD conversion. Our prognosis prediction model using the potential blood-based biomarkers for early AD diagnosis, which combined two immune repertoires (IGK and TRA), WDR37, and clinical information, successfully classified MCI patients into two groups, low and high, in terms of risk of MCI-to-AD conversion (log-rank test P = 2.57e-3). It achieved a concordance index of 0.694 in a discovery cohort and of 0.643 in an independent validation cohort. We believe that further investigation, using larger sample sizes, will lead to practical clinical use in the near future.
ArticleNumber 15
Author Shigemizu, Daichi
Mitsumori, Risa
Niida, Shumpei
Ozaki, Kouichi
Akiyama, Shintaro
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Snippet Mild cognitive impairment (MCI) is a clinical precursor of Alzheimer’s disease (AD). Recent genetic studies have reported on associations between AD risk genes...
Mild cognitive impairment (MCI) is a clinical precursor of Alzheimer's disease (AD). Recent genetic studies have reported on associations between AD risk genes...
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SourceType Open Access Repository
Aggregation Database
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StartPage 15
SubjectTerms 631/378/2611
692/499
692/53
692/699/375/132/1283
Aging
Alzheimer's disease
B-cell receptor
Biomarkers
Biomedical and Life Sciences
Biomedicine
Cell Physiology
Cognitive ability
Diagnosis
Geriatrics/Gerontology
Heavy chains
Human Physiology
Immunoglobulins
Leukocytes (neutrophilic)
Lymphocytes B
Lymphocytes T
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Title Identification of potential blood biomarkers for early diagnosis of Alzheimer’s disease through immune landscape analysis
URI https://link.springer.com/article/10.1038/s41514-022-00096-9
https://www.proquest.com/docview/2731947542
https://www.proquest.com/docview/2732542091
https://pubmed.ncbi.nlm.nih.gov/PMC9636153
Volume 8
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