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Apolipoprotein E particle size is increased in Alzheimer's disease.

ABSTRACT: Introduction:Apolipoprotein E4 (apoE4) is the predominant risk factor for late-onset Alzheimer's disease (AD), but the question of which structural differences might explain its effect remains unclear. Methods:We compared high-density lipoprotein-like apoE particles from 12 AD and 10 control patients using size-exclusion chromatography. Results:ApoE particles from patients genotyped as ?4/?4 were 2.2 ± 0.3 times as massive as particles from ?3/?3 control subjects and 1.4 ± 0.1 times as massive as particles from ?3/?3 AD patients. The increased particle size was not because of incorporation of amyloid ? or apoE proteolysis products. Particles from AD patients genotyped as ?3/?3 were 1.59 ± 0.27 times as massive as ?3/?3 control subjects. Discussion:Increased particle size in AD is affected by A PO E genotype and by disease-related differences in assembly or stability. These differences suggest that lipoprotein assembly or stability in AD brain plays an important role in determining apoE4 pathogenicity.

SUBMITTER: Nelson TJ

PROVIDER: S-EPMC6293020 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Apolipoprotein E particle size is increased in Alzheimer's disease.

Nelson Thomas J TJ Sen Abhik A

Alzheimer's & dementia (Amsterdam, Netherlands) 20181113

<h4>Introduction</h4>Apolipoprotein E4 (apoE4) is the predominant risk factor for late-onset Alzheimer's disease (AD), but the question of which structural differences might explain its effect remains unclear.<h4>Methods</h4>We compared high-density lipoprotein-like apoE particles from 12 AD and 10 control patients using size-exclusion chromatography.<h4>Results</h4>ApoE particles from patients genotyped as ε4/ε4 were 2.2 ± 0.3 times as massive as particles from ε3/ε3 control subjects and 1.4 ± ...[more]

PMID: 30581971

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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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Apolipoprotein E particle size is increased in Alzheimer's disease.

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Apolipoprotein E particle size is increased in Alzheimer's disease.

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