APOE É4 dose associates with increased brain iron and ß-amyloid via blood-brain barrier dysfunction.
J Neurol Neurosurg Psychiatry
; 2022 Apr 28.
Article
in En
| MEDLINE
| ID: mdl-35483916
ABSTRACT
OBJECTIVE:
To examine the effect of apolipoprotein E (APOE) É4 dose on blood-brain barrier (BBB) clearance function, evaluated using an advanced MRI technique and analyse its correlation with brain iron and ß-amyloid accumulation in the early stages of the Alzheimer's continuum.METHODS:
In this single-centre observational prospective cohort study, 24 APOE É4 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 (kw). Participants also underwent quantitative susceptibility mapping, [11C]Pittsburgh compound B-positron emission tomography and neuropsychological testing. Using an atlas-based approach, we compared the regional kw of the whole brain among the groups and analysed its correlation with the neuroradiological and neuropsychological findings.RESULTS:
The BBB kw values in the neocortices differed significantly among the groups (APOE É4 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), ß-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 É4 dose.INTERPRETATION:
Our results suggest that an increased APOE É4 dose is associated with decreased effective brain-waste clearance, such as iron and ß-amyloid, through the BBB.
Full text:
1
Database:
MEDLINE
Type of study:
Observational_studies
/
Risk_factors_studies
Language:
En
Year:
2022
Type:
Article