Dataset Information

Increased apolipoprotein E and decreased TNF-? in the cerebrospinal fluid of nondemented APOE-?4 carriers.

ABSTRACT: Aim: The ?4 allele of apolipoprotein E gene (APOE) is a well-known risk factor of late-onset Alzheimer's disease. However, little is known why this variant confers a risk for Alzheimer's disease. The aim of this study was to examine the influence of the APOE genotype on cerebrospinal fluid (CSF) protein levels.

Methods: The present study performed a secondary analysis on our previously generated database to compare the CSF levels of 1128 proteins between APOE-?4 carriers (28 subjects) and noncarriers (104 subjects). All subjects were physically healthy Japanese individuals without dementia.

Results: CSF levels of apoE2, apoE3, and apoE4 were significantly higher (all nominal P < 10 × 10^-5 , false discovery rate < 0.001) and those of tumor necrosis factor-? (TNF-?) were significantly lower (nominal P = 1.39 × 10^-6 , false discovery rate < 0.001) in APOE-?4 carriers than in noncarriers. No significant correlation was observed between the CSF levels of TNF-? and any of the apoE proteins.

Conclusions: Our findings indicate the possible roles of apoE and TNF-? in the pathogenesis of APOE-?4-associated Alzheimer's disease.

SUBMITTER: Sasayama D

PROVIDER: S-EPMC7722685 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Increased apolipoprotein E and decreased TNF-α in the cerebrospinal fluid of nondemented APOE-ε4 carriers.

Sasayama Daimei D Hattori Kotaro K Yokota Yuuki Y Matsumura Ryo R Teraishi Toshiya T Yoshida Sumiko S Kunugi Hiroshi H

Neuropsychopharmacology reports 20200519 2

<h4>Aim</h4>The ε4 allele of apolipoprotein E gene (APOE) is a well-known risk factor of late-onset Alzheimer's disease. However, little is known why this variant confers a risk for Alzheimer's disease. The aim of this study was to examine the influence of the APOE genotype on cerebrospinal fluid (CSF) protein levels.<h4>Methods</h4>The present study performed a secondary analysis on our previously generated database to compare the CSF levels of 1128 proteins between APOE-ε4 carriers (28 subject ...[more]

PMID: 32426945

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Project description: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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Dataset Information

Increased apolipoprotein E and decreased TNF-? in the cerebrospinal fluid of nondemented APOE-?4 carriers.

Publications

Increased apolipoprotein E and decreased TNF-α in the cerebrospinal fluid of nondemented APOE-ε4 carriers.

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