Increased plasma and brain immunoglobulin A in Alzheimer’s disease is lost in apolipoprotein E ε4 carriers
Pocevičiūtė, Dovilė LU
; Nuñez-Diaz, Cristina
LU
; Roth, Bodil
LU
; Janelidze, Shorena
LU
; Giannisis, Andreas
; Hansson, Oskar
LU
and Wennström, Malin
LU
(2022)
In Alzheimer's Research and Therapy
14(1).
- Abstract
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... (More)
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.
(Less)
- author
- Pocevičiūtė, Dovilė
LU
; Nuñez-Diaz, Cristina
LU
; Roth, Bodil
LU
; Janelidze, Shorena
LU
; Giannisis, Andreas
; Hansson, Oskar
LU
and Wennström, Malin
LU
- author collaboration
- organization
- publishing date
- 2022-12-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Amyloid beta, Blood-brain barrier, Immunoglobulin, Inflammation
- in
- Alzheimer's Research and Therapy
- volume
- 14
- issue
- 1
- article number
- 117
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:36008818
- scopus:85137100900
- ISSN
- 1758-9193
- DOI
- 10.1186/s13195-022-01062-z
- language
- English
- LU publication?
- yes
- id
- 2be2589e-421d-4846-8006-2307f0151fb2
- date added to LUP
- 2022-10-14 11:49:56
- date last changed
- 2024-04-18 14:58:41
@article{2be2589e-421d-4846-8006-2307f0151fb2,
abstract = {{<p>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.</p>}},
author = {{Pocevičiūtė, Dovilė and Nuñez-Diaz, Cristina and Roth, Bodil and Janelidze, Shorena and Giannisis, Andreas and Hansson, Oskar and Wennström, Malin}},
issn = {{1758-9193}},
keywords = {{Amyloid beta; Blood-brain barrier; Immunoglobulin; Inflammation}},
language = {{eng}},
month = {{12}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{Alzheimer's Research and Therapy}},
title = {{Increased plasma and brain immunoglobulin A in Alzheimer’s disease is lost in apolipoprotein E ε4 carriers}},
url = {{http://dx.doi.org/10.1186/s13195-022-01062-z}},
doi = {{10.1186/s13195-022-01062-z}},
volume = {{14}},
year = {{2022}},
}