ArticleAlzheimer's research & therapy2022
Increased plasma and brain immunoglobulin A in Alzheimer's disease is lost in apolipoprotein E ε4 carriers.
Article in Alzheimer's research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Review
- Article
- Perivascular phosphorylated TDP-43 inclusions are associated with Alzheimer's disease pathology and loss of CD146 and Aquaporin-4.Brain pathology (Zurich, Switzerland) · 2025Article
- Biomarker understanding first lessons from drug development for IgA-driven autoimmune and fibrotic diseases.Cambridge prisms. Precision medicine · 2025Review
- The Effect of APOE ε4 on Alzheimer's Disease Fluid Biomarkers: A Cross-Sectional Study Based on the COAST.CNS neuroscience & therapeutics · 2025Observational
- Autoantibody profiles in Alzheimer´s, Parkinson´s, and dementia with Lewy bodies: altered IgG affinity and IgG/IgM/IgA responses to alpha-synuclein, amyloid-beta, and tau in disease-specific pathological patterns.Journal of neuroinflammation · 2024Article
- Effects of Intestinal M Cells on Intestinal Barrier and Neuropathological Properties in an AD Mouse Model.Molecular neurobiology · 2024Article
- Review
- Okinawa-Based Nordic Diet Decreases Plasma Levels of IAPP and IgA against IAPP Oligomers in Type 2 Diabetes Patients.International journal of molecular sciences · 2024Article
- Gut microbiota and circadian rhythm in Alzheimer's disease pathophysiology: a review and hypothesis on their association.npj aging · 2023Review
- Plasma IAPP-Autoantibody Levels in Alzheimer's Disease Patients Are Affected byInternational journal of molecular sciences · 2023Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlzheimer'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.
methodsIgA 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.
resultsPlasma 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.
conclusionsOur 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.
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