IC‐P‐140: Apolipoprotein E genotype influences spatial distribution of cerebral microbleeds

Abstract

35m x 35m x 39m, corpus callosum (CC) and cortical thicknesses were measured. Diffusion tensor imaging (DTI) was performed using TR/TE 2500ms/ 27ms, slice thickness 500mm, in-plane resolution 59mm x 59mm, 10 slices, 64 gradient directions and one b value per direction. Fractional anisotropy (FA) was calculated from CC, dorsal and ventral blades of dentate gyrus molecular layer (dDGML and vDGML) in the dorsal hippocampus, and dentate gyrus polymorphic layer (DGP). Results: Cortical thickness measured at the level of association cortex was 32% smaller in the floxPS1/PS2ko/cre mouse brains. Reduced cortical thickness probably represents fewer neurons in the cre mice. Thickness of CC also was reduced in these mice by 43%. DTI-measured FA in CC was lower by 46%. Thinner CC together with lower FA reflects axonal abnormalities in cre mice. FA in dDGML was significantly higher in cre mice compared to control mice, which suggests increased dendritic density based on our previous findings. There was no difference between the two groups of mice in FA measured in vDGML and DGP. Conclusions: High resolution MR imaging reveals neuronal, axonal and dendritic alterations in mice with PS1 and PS2 deletions from the adult forebrain.Background: Cerebral amyloid angiopathy (CAA) is a major cause of intracerebral hemorrhage in the elderly and is a frequent coexisting pathology in p ersons with Alzheimer's disease (AD). Like in AD, the apolipoprotein E (APOE) genotype is a known risk factor for CAA-related hemorrhages, and lobar microbleeds are a diagnostic hallmark of CAA. Within CAA patients, microbleeds tend to cluster and typically occur in the occipital lobe. Microbleeds also frequently occur in asymptomatic persons, suggesting that underlying CAA is present in these persons as well. To support this hypothesis, we investigated, in the general population, whether incident microbleeds occur in close proximity to prevalent microbleeds and whether APOE genotype affects spatial distribution of microbleeds. Methods: In 292 participants from a population-based study, all with microbleeds, we manually labeled all microbleeds on baseline and follow-up MR-scans. To analyze proximity, we calculated the distance between each incident microbleed and the nearest prevalent microbleed within and between persons. To analyze lobar distribution, we performed automated lobar brain segmentation on all labeled images. Subsequently, we investigated the proximity and lobar distribution of microbleeds in strata of APOE genotypes. Results: Incident and prevalent microbleeds occurred in significantly closer proximity within persons than between persons (19.0 6 18.0mm versus 61.2 6 28.2mm; p < 0.001). Proximity was influenced by APOE genotype. Compared to persons with APOE e3e3, incident microbleeds occurred, on average, 1 6.2 mm (95% CI for difference 9.1-23.3, p<0.001) and 23.3 mm (95% CI for difference 17.4-29.2, p<0.0001) closer to prevalent microbleeds in APOE e2 carriers and APOE e4 allele carriers, respectively. As expected, lobar microbleeds in the ...

Cerebral microbleeds: Spatial distribution implications

“…The described posterior distribution of beta-amyloid deposition [6,9], lobar ICH [17,20]. Our most recent work also showed that among all microbleeds, incident microbleeds occurred in close proximity to prevalent microbleeds within participants, particularly among APOE risk allele carriers [20]. Though the microbleeds in this analysis were primarily lobar, we did observe clustering between microbleeds that technically fell on opposite sides of regional boundaries, i.e., deep and lobar (Figure 1) [20].…”

“…Thus, these two alleles seem to result in distinct pathways, both of which are more susceptible to hemorrhagic outcomes compared to the wild-type genotype. The described posterior distribution of beta-amyloid deposition [6,9], lobar ICH [17,20]. Our most recent work also showed that among all microbleeds, incident microbleeds occurred in close proximity to prevalent microbleeds within participants, particularly among APOE risk allele carriers [20].…”

“…In a recent paper, posterior distribution of lobar microbleeds within the entire communitydwelling Rotterdam Study population was found, but those among this population, who were carriers of the APOE e2 or e4 alleles, had microbleeds that occurred closer together and had an ever higher proportion of microbleeds in the occipital lobe compared to persons with APOE e3e3 genotype [20].…”

Cerebral Microbleeds, Vascular Risk Factors, and Magnetic Resonance Imaging Markers: The Northern Manhattan Study

“…13 Location and distribution of CMBs also may relate to the apolipoprotein E (APOE) genotype, and racial and ethnic variations are poorly understood. 1,14 The majority of studies of CMB prevalence and risk factors were done in samples that do not include blacks or Hispanics/ Latinos, who may be at higher risk of stroke 15 and dementia. 16 We have previously found that blacks and Hispanics have a greater incidence of stroke than non-Hispanic whites 15 and that the impact of stroke risk factors differs by race and ethnicity.…”

Background and distribution of lobar microbleeds in cognitive dysfunction

“…First, the sample size was relatively small and statistical power was therefore limited. Second, we did not investigate Apo E genotype, which influences the spatial distribution of CMBs (Loehrer et al, 2014). Finally, we did not examine useful biomarkers for vascular amyloid deposition, including amyloid imaging and Aβ 40 and Aβ 42 values in cerebrospinal fluid (Dierksen et al, 2010;Renald et al, 2012).…”