<i>APOE</i>
            ε2/ε4 polymorphism and cerebral microbleeds on gradient-echo MRI

Kim, M.; Bae, Hee Joon; Lee, J.; Kang, Le; Lee, S.; Kim, S.; Lee, J. E.; Lee, K. M.; Yoon, Byung‐Woo; Kwon, Ohyun; Koo, Ja Seong; Kim, B. K.

doi:10.1212/01.wnl.0000183311.48144.7f

Cited by 36 publications

(30 citation statements)

References 8 publications

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“…Incidence rates in AD have not been reported to date; however, the incidence of microbleeds (any site) in acute stroke has been reported to be 0.8/y, increasing to 5.4/y in those with $5 microbleeds at baseline. 13 In cross-sectional studies, LMBs have been associated with increasing age, 7,34 presence of APOE e2 35 and APOE e4, 5,34,36 and high PiB retention on PET imaging. 7 Over longitudinal follow-up, incident LMBs have also been associated with the presence of baseline microbleeds and severity of white matter disease.…”

Section: Resultsmentioning

confidence: 99%

Incidence of cerebral microbleeds in preclinical Alzheimer disease

et al. 2014

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Objective: We sought to determine the incidence and associations of lobar microbleeds (LMBs) in a longitudinal cohort with 11 C-Pittsburgh compound B (PiB) PET imaging.Methods: One hundred seventy-four participants from the observational Australian Imaging, Biomarkers and Lifestyle Study of Ageing (97 with normal cognition [NC], 37 with mild cognitive impairment [MCI], and 40 with Alzheimer disease [AD] dementia) were assessed at 3 time points over 3 years with 3-tesla susceptibility-weighted MRI and 11 C-PiB PET. MRIs were inspected for microbleeds, siderosis, infarction, and white matter hyperintensity severity, blind to clinical and PiB findings. Neocortical PiB standardized uptake value ratio, normalized to cerebellar cortex, was dichotomized as positive or negative (PiB1/2, standardized uptake value ratio .1.5). Annualized LMB incidence was calculated, and logistic regression was used to determine the association of incident LMBs with PiB, APOE e41 status, and cerebrovascular disease.Results: LMBs were present in 18.6% of NC, 24.3% of MCI, and 40% of AD participants (p , 0.05 vs NC). LMB incidence was 0.2 6 0.6 per year in NC participants, 0.2 6 0.5 in MCI, and 0.7 6 1.4 in AD (p , 0.03 vs NC) and was 6-fold higher in PiB1 than PiB-NC. Incident LMBs were associated with age, APOE e41, PiB1, and baseline LMBs. Incidence of multiple LMBs was also associated with lacunar infarction and white matter hyperintensity severity. Conclusions:Older age, baseline LMBs, higher b-amyloid burden, and concomitant cerebrovascular disease may all confer higher risk of incident LMBs. This should be considered when designing protocols for amyloid-modifying clinical trials. Neurology ® 2014;82:1266-1273 GLOSSARY Ab 5 b-amyloid; AD 5 Alzheimer disease; AIBL 5 Australian Imaging, Biomarkers and Lifestyle Study of Ageing; CAA 5 cerebral amyloid angiopathy; CI 5 confidence interval; FLAIR 5 fluid-attenuated inversion recovery; GRE 5 gradient-recall echo; LMB 5 lobar microbleed; MCI 5 mild cognitive impairment; MP-RAGE 5 magnetization-prepared rapid-acquisition gradient echo; NC 5 normal cognition; OR 5 odds ratio; PiB 5 Pittsburgh compound B; SS 5 superficial siderosis; SUVR 5 standardized uptake value ratio; SWI 5 susceptibility-weighted imaging; TE 5 echo time; TR 5 repetition time; VRF 5 vascular risk factor; WMH 5 white matter hyperintensity.

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Section: Resultsmentioning

confidence: 99%

Incidence of cerebral microbleeds in preclinical Alzheimer disease

et al. 2014

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“…Seven studies which included 7,272 participants (99% of the total) presented dichotomous data for BMBs (i.e., presence vs absence per genotype or group of genotypes), enabling their results to be pooled in meta-analyses. 2,3,[16][17][18][19][20][21] The remaining 3 presented continuous data (i.e., mean number of BMBs per genotype) or purely qualitative statements about the association between APOE and BMBs. [22][23][24] Study characteristics.…”

Section: Resultsmentioning

confidence: 99%

“…Most participants were of European origin, but one study was conducted in Asians. 17 Participants were middle-aged to elderly (mean age per study ranged from 45 to 76 years). Studies had a mean of 735 (range 20 to 3,689) participants.…”

Section: Resultsmentioning

confidence: 99%

10 Genetic associations with brain microbleeds: systematic review and meta-analyses

Sudlow

Maxwell

Jackson

et al. 2011

Journal of Neurology, Neurosurgery & Psychiatry

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Objective: We performed a systematic review and meta-analyses to assess the evidence for genetic associations with brain microbleeds (BMBs). Methods:We sought all published studies of the association between any genetic polymorphism and BMBs studied in a total of Ͼ100 people. We critically appraised studies, and calculated pooled odds ratios (ORs) using the generic inverse variance fixed effects method. We used I 2 and 2 statistics to assess heterogeneity, and fail-safe N estimates to assess the robustness of our results. Results:Only the APOE ⑀2/3/4 polymorphism had been studied in Ͼ100 people (10 studies, Conclusions:Given the known associations of APOE alleles with lobar intracerebral hemorrhage and cerebral amyloid angiopathy, these findings support the concept that strictly lobar BMBs may be an imaging biomarker of cerebral amyloid angiopathy. Neurology ® 2011;77:158-167 GLOSSARY BMB ϭ brain microbleed; CAA ϭ cerebral amyloid angiopathy; CI ϭ confidence interval; GRE ϭ gradient-recalled echo; HWE ϭ Hardy-Weinberg equilibrium; ICH ϭ intracerebral hemorrhage; OR ϭ odds ratio.Brain microbleeds (BMBs) are minute deposits of blood products, seen as focal areas of signal loss typically Ͻ10 mm in diameter on haem-sensitive T2*-weighted gradient-recalled echo (GRE) MRI sequences. BMBs occur in 5% to 38% of apparently healthy people, increasing in frequency with age, hypertension, and smoking.

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“…APOE gene polymorphisms have been widely investigated in the fields of neurovascular disease and stroke. 9,13,21,24,29 According to a recent systematic review, APOE ε4 allele carrier status was associated with white matter hyperintensity burden and lobar microbleeds in cerebrovascular disease. 24 However, APOE ε2 allele carrier status was associated with white matter hyperintensity and the risk of brain infarcts.…”

Section: Discussionmentioning

confidence: 99%

“…24 In a hospital-based, multicenter study of cerebral microbleeds and APOE gene polymorphisms in Korean patients who had suffered strokes, the presence of the APOE ε2 or ε4 allele was associated with lobar microbleeds but not with nonlobar microbleeds. 13 The APOE ε2 allele is known to be associated with fibrinoid necrosis, and the APOE ε4 allele has been associated with the loss of smooth muscle and vessel wall thickness, as well as with vascular Ab deposition. 2,16,28 Although there was no difference in APOE genotype between patients with MMD and the control group (Table 1), our results revealed a difference in APOE genotype according to the presence of microbleeds (Fig.…”

Section: Discussionmentioning

confidence: 99%

Association of apolipoprotein E gene polymorphism with small-vessel lesions and stroke type in moyamoya disease: a preliminary study

Jang

Huh

Lee

2016

JNS

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M oyaMoya disease (MMD) is a progressive cerebrovascular occlusive disorder consisting of bilateral stenosis or occlusion of the supraclinoid internal carotid artery (ICA) and its major branches, with net-like vessels in the area surrounding the circle of Willis. 27 Many studies have demonstrated a higher prevalence of asymptomatic cerebral microbleeds in patients with MMD compared with the normal population.11 In addition, a recent meta-analysis showed that a high incidence of asymptomatic cerebral microbleeds appeared to be correlated with the hemorrhagic onset type in patients with MMD.20 Kikuta et al. 12 identified the presence of multiple microbleeds as a predictor of subsequent hemorrhages in patients with MMD.abbreviatioNs APOE = apolipoprotein E; GRE = gradient-recalled echo; ICA = internal carotid artery; MMD = moyamoya disease; SVL = small-vessel lesion; T2WI = T2*-weighted imaging. obJective The present study was conducted to investigate whether microbleeds or microinfarcts are associated with apolipoprotein E (APOE) gene polymorphisms in patients with moyamoya disease (MMD), and if so, whether APOE gene polymorphisms are also associated with stroke type in patients with MMD. methods This cross-sectional, multicenter study included 86 consecutive patients with MMD who underwent T2*-weighted gradient echo or susceptibility-weighted MR imaging and 83 healthy control volunteers. Baseline clinical and radiological characteristics were recorded at diagnosis, and inter- and intragroup differences in the APOE genotypes were assessed. Multivariate binary logistic regression models were used to determine the association factors for smallvessel lesions (SVLs) and hemorrhagic presentation in patients with MMD. results There was no difference in APOE gene polymorphism and the incidence of SVLs between patients with MMD and healthy controls (p > 0.05). In the MMD group, 7 (8.1%) patients had microbleeds and 32 (37.2%) patients had microinfarcts. Microbleeds were more frequently identified in patients with hemorrhagic-type than in nonhemorrhagictype MMD (p = 0.003). APOE genotypes differed according to the presence of microbleeds (p = 0.024). APOE ε2 or ε4 carriers also experienced microbleeds more frequently than APOE ε3/ε3 carriers (p = 0.013). In the multivariate regression analysis in patients with MMD, microbleeds were significantly related to APOE ε2 or ε4 carrier status (OR 7.86;; p = 0.032) and cerebral aneurysm (OR 17.31; 95% CI 2.09-143.57; p = 0.008). Microinfarcts were independently associated with hypertension (OR 3.01; 95% CI 1.05-7.86; p = 0.007). Hemorrhagic presentation was markedly associated with microbleeds (OR 10.63; 95% CI 1.11-102.0; p = 0.041). coNclusioNs These preliminary results did not show a difference in APOE gene polymorphisms between patients with MMD and healthy persons. However, they imply that APOE gene polymorphisms may play certain roles in the presence of microbleeds but not microinfarcts in patients with MMD. A further confirmatory study is necessary to elucidate the effec...

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APOE ε2/ε4 polymorphism and cerebral microbleeds on gradient-echo MRI

Cited by 36 publications

References 8 publications

Incidence of cerebral microbleeds in preclinical Alzheimer disease

Incidence of cerebral microbleeds in preclinical Alzheimer disease

10 Genetic associations with brain microbleeds: systematic review and meta-analyses

Association of apolipoprotein E gene polymorphism with small-vessel lesions and stroke type in moyamoya disease: a preliminary study

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