☆ 4.6 Article

APOE ε4 dose associates with increased brain iron and β-amyloid via blood-brain barrier dysfunction

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2022)

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JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY

卷 93, 期 7, 页码 772-778

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BMJ PUBLISHING GROUP

DOI: 10.1136/jnnp-2021-328519

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Clinical Neurology Psychiatry Surgery

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24th General Assembly of the Japanese Association of Medical Sciences
Kowa Life Science Foundation

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The study aimed to examine the effect of APOE ε4 dose on BBB clearance function and its correlation with brain iron and beta-amyloid accumulation. The results showed that increased APOE ε4 dose was associated with decreased effective brain-waste clearance through the BBB.

Objective To examine the effect of apolipoprotein E (APOE) epsilon 4 dose on blood-brain barrier (BBB) clearance function, evaluated using an advanced MRI technique and analyse its correlation with brain iron and beta-amyloid accumulation in the early stages of the Alzheimer's continuum. Methods In this single-centre observational prospective cohort study, 24 APOE epsilon 4 non-carriers, 22 heterozygotes and 20 homozygotes in the early stages of the Alzheimer's continuum were scanned with diffusion-prepared arterial spin labelling, which estimates the water exchange rate across the BBB (k(w)). Participants also underwent quantitative susceptibility mapping, [C-11] Pittsburgh compound B-positron emission tomography and neuropsychological testing. Using an atlas-based approach, we compared the regional k(w) of the whole brain among the groups and analysed its correlation with the neuroradiological and neuropsychological findings. Results The BBB k(w) values in the neocortices differed significantly among the groups (APOE epsilon 4 non-carriers> heterozygotes>homozygotes). These values correlated with brain iron levels (frontal lobe: r=-0.476, 95% CI=-0.644 to -0.264, p=0.011; medial temporal lobe: r=-0.455, 95% CI=-0.628 to -0.239, p=0.017), P-amyloid loads (frontal lobe: r=-0.504, 95%CI=-0.731 to -0.176, p=0.015; medial temporal lobe: r=-0.452, 95% CI=-0.699 to -0.110, p=0.036) and neuropsychological scores, after adjusting for age, sex and APOE epsilon 4 dose. Interpretation Our results suggest that an increased APOE epsilon 4 dose is associated with decreased effective brain-waste clearance, such as iron and beta-amyloid, through the BBB.

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Increased plasma and brain immunoglobulin A in Alzheimer's disease is lost in apolipoprotein E ε4 carriers

Dovile Poceviciute, Cristina Nunez-Diaz, Bodil Roth, Shorena Janelidze, Andreas Giannisis, Oskar Hansson, Malin Wennstrom

Summary: Alzheimer's disease is characterized by Aβ plaques, NFT, and neuroinflammation, but recent studies suggest that peripheral inflammation might also play a role. This study found that plasma IgA levels were higher in AD patients, especially in APOE ε4 non-carriers, and these levels were associated with cognitive decline and neuropathology. This suggests that the relationship between AD pathology and plasma IgA levels may be influenced by APOE allele status.

ALZHEIMERS RESEARCH & THERAPY (2022)