Increased plasma and brain immunoglobulin A in Alzheimer's disease is lost in apolipoprotein E ε4 carriers.
Alzheimer Disease
/ cerebrospinal fluid
Amyloid beta-Peptides
/ cerebrospinal fluid
Apolipoprotein E4
/ genetics
Apolipoproteins E
/ metabolism
Biomarkers
/ cerebrospinal fluid
Brain
/ metabolism
Humans
Immunoglobulin A
/ metabolism
Peptide Fragments
/ cerebrospinal fluid
tau Proteins
/ cerebrospinal fluid
Amyloid beta
Blood-brain barrier
Immunoglobulin
Inflammation
Journal
Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643
Informations de publication
Date de publication:
26 08 2022
26 08 2022
Historique:
received:
03
06
2022
accepted:
15
08
2022
entrez:
25
8
2022
pubmed:
26
8
2022
medline:
30
8
2022
Statut:
epublish
Résumé
Alzheimer's disease (AD) is foremost characterized by β-amyloid (Aβ)-extracellular plaques, tau-intraneuronal fibrillary tangles (NFT), and neuroinflammation, but over the last years it has become evident that peripheral inflammation might also contribute to the disease. AD patients often demonstrate increased levels of circulating proinflammatory mediators and altered antibody levels in the blood. In our study, we investigated the plasma Immunoglobulin A (IgA) levels in association with apolipoprotein E (APOE) ε4 status and Aβ pathology. IgA levels in antemortem-collected (cohort I) and postmortem-collected (cohort II) plasma samples from AD patients (n = 30 in cohort I and n = 16 in cohort II) and non-demented age-matched controls (NC) (n = 42 in cohort I and n = 7 in cohort II) were measured using ELISA. Hippocampal sections from cohort II were immunostained against IgA, and the IgA area fraction as well as the number of IgA positive (IgA+) cells in the cornu ammonis region were analysed using ImageJ. The relationship between plasma IgA levels and cognition, C-reactive protein (CRP), and cerebrospinal fluid (CSF) AD biomarkers in cohort I as well as neuropathology, IgA+ cell number, and IgA area fraction in cohort II was analysed before and after grouping the cohorts into APOEε4 carriers and APOEε4 non-carriers. Plasma IgA levels were higher in AD patients compared to NC in both cohorts. Also, AD patients demonstrated higher IgA area fraction and IgA+ cell number compared to NC. When APOEε4 status was considered, higher plasma IgA levels in AD patients were only seen in APOEε4 non-carriers. Finally, plasma IgA levels, exclusively in APOEε4 non-carriers, were associated with cognition, CRP, and CSF Aβ levels in cohort I as well as with IgA area fraction, IgA+ cell number, and Aβ, Lewy body, and NFT neuropathology in cohort II. Our study suggests that AD pathology and cognitive decline are associated with increased plasma IgA levels in an APOE allele-dependent manner, where the associations are lost in APOEε4 carriers.
Sections du résumé
BACKGROUND
Alzheimer's disease (AD) is foremost characterized by β-amyloid (Aβ)-extracellular plaques, tau-intraneuronal fibrillary tangles (NFT), and neuroinflammation, but over the last years it has become evident that peripheral inflammation might also contribute to the disease. AD patients often demonstrate increased levels of circulating proinflammatory mediators and altered antibody levels in the blood. In our study, we investigated the plasma Immunoglobulin A (IgA) levels in association with apolipoprotein E (APOE) ε4 status and Aβ pathology.
METHODS
IgA levels in antemortem-collected (cohort I) and postmortem-collected (cohort II) plasma samples from AD patients (n = 30 in cohort I and n = 16 in cohort II) and non-demented age-matched controls (NC) (n = 42 in cohort I and n = 7 in cohort II) were measured using ELISA. Hippocampal sections from cohort II were immunostained against IgA, and the IgA area fraction as well as the number of IgA positive (IgA+) cells in the cornu ammonis region were analysed using ImageJ. The relationship between plasma IgA levels and cognition, C-reactive protein (CRP), and cerebrospinal fluid (CSF) AD biomarkers in cohort I as well as neuropathology, IgA+ cell number, and IgA area fraction in cohort II was analysed before and after grouping the cohorts into APOEε4 carriers and APOEε4 non-carriers.
RESULTS
Plasma IgA levels were higher in AD patients compared to NC in both cohorts. Also, AD patients demonstrated higher IgA area fraction and IgA+ cell number compared to NC. When APOEε4 status was considered, higher plasma IgA levels in AD patients were only seen in APOEε4 non-carriers. Finally, plasma IgA levels, exclusively in APOEε4 non-carriers, were associated with cognition, CRP, and CSF Aβ levels in cohort I as well as with IgA area fraction, IgA+ cell number, and Aβ, Lewy body, and NFT neuropathology in cohort II.
CONCLUSIONS
Our study suggests that AD pathology and cognitive decline are associated with increased plasma IgA levels in an APOE allele-dependent manner, where the associations are lost in APOEε4 carriers.
Identifiants
pubmed: 36008818
doi: 10.1186/s13195-022-01062-z
pii: 10.1186/s13195-022-01062-z
pmc: PMC9414424
doi:
Substances chimiques
Amyloid beta-Peptides
0
Apolipoprotein E4
0
Apolipoproteins E
0
Biomarkers
0
Immunoglobulin A
0
Peptide Fragments
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
117Informations de copyright
© 2022. The Author(s).
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