Dataset Information

The roles of apolipoprotein E ε4 on neuropathology and neuroinflammation in patients with Alzheimer's disease.

ABSTRACT:

Aims

To explore the roles of apolipoprotein E (APOE) ε4 on the neuropathology and neuroinflammation in Alzheimer's disease (AD) patients.

Methods

AD patients were divided into the APOE ε4 carrier and the APOE ε4 non-carrier groups according to APOE genotype. Demographic information, cognitive function, the levels of neuropathological proteins and neuroinflammatory factors in cerebrospinal fluid (CSF) were compared between the two groups, and their correlations were subsequently analyzed.

Results

β amyloid protein (Aβ)_1-42 level from the APOE ε4 carrier group was significantly lower than that from the non-carrier group (p = 0.023), which was associated with worse cognitive function. The nitric oxide (NO) level was significantly elevated in the APOE ε4 carrier group compared to the non-carrier group (p = 0.016), which was significantly and positively correlated with the Trail Making Test (TMT)-A-time (r = 0.21, p = 0.026) and TMT-B-time (r = 0.38, p < 0.01).

Conclusion

APOE ε4 is associated with poorer cognition, particularly the early symptoms of memory, language, and attention. APOE ε4 is associated with lower Aβ_1-42 level, and the more numbers of APOE ε4 are carried, the lower level of Aβ_1-42 is measured. APOE ε4 is associated with elevated NO level, which is linked to the impaired attention and executive function.

SUBMITTER: He M

PROVIDER: S-EPMC10916449 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

The roles of apolipoprotein E ε4 on neuropathology and neuroinflammation in patients with Alzheimer's disease.

He Mingyue M Lian Tenghong T Guo Peng P Zhang Weijiao W Zhang Yanan Y Huang Yue Y Liu Gaifen G Guan Huiying H Li Jinghui J Luo Dongmei D Zhang Weijia W Zhang Wenjing W Qi Jing J Yue Hao H Wang Xiaomin X Zhang Wei W

CNS neuroscience & therapeutics 20230912 3

<h4>Aims</h4>To explore the roles of apolipoprotein E (APOE) ε4 on the neuropathology and neuroinflammation in Alzheimer's disease (AD) patients.<h4>Methods</h4>AD patients were divided into the APOE ε4 carrier and the APOE ε4 non-carrier groups according to APOE genotype. Demographic information, cognitive function, the levels of neuropathological proteins and neuroinflammatory factors in cerebrospinal fluid (CSF) were compared between the two groups, and their correlations were subsequently an ...[more]

PMID: 37697966

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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

The roles of apolipoprotein E ε4 on neuropathology and neuroinflammation in patients with Alzheimer's disease.

Aims

Methods

Results

Conclusion

Publications

The roles of apolipoprotein E ε4 on neuropathology and neuroinflammation in patients with Alzheimer's disease.

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