APOE genotype and MRI markers of cerebrovascular disease

Abstract

Objective: We aimed to examine the association of APOE e genotype with MRI markers of cerebrovascular disease (CVD): white matter hyperintensities, brain infarcts, and cerebral microbleeds.Methods: We performed a systematic review and meta-analysis of 42 cross-sectional or longitudinal studies identified in PubMed from 1966 to June 2012 (n 5 29,965). This included unpublished data from 3 population-based studies: 3C-Dijon, Framingham Heart Study, and Sydney Memory and Ageing Study. When necessary, authors were contacted to provide effect estimates for the meta-analysis. Conclusions: APOE e4 and APOE e2 were associated with increasing burden in MRI markers for both hemorrhagic and ischemic CVD. While the association of APOE e4 with an increased burden of CVD could be partly contributing to the relationship between APOE e4 and AD, APOE e2 was associated with MRI markers of CVD in the opposite direction compared to AD. The e4 allele of the APOE gene is a major risk factor for dementia and Alzheimer disease (AD). Results 1-6The association of APOE with cerebrovascular disease (CVD) is more controversial.7 APOE e4 is a risk factor for cerebral amyloid angiopathy (CAA), a major determinant of intracerebral hemorrhage (ICH) in older individuals.1 Recent data from the International Stroke Genetics Consortium suggest an association of APOE e4 with an increased risk of ICH, mostly lobar, 8 and an association of the APOE e2 allele with an increased risk and size of lobar ICH. 8,9 Whether the epsilon polymorphism is also associated with an increased risk of ischemic stroke and MRI markers of CVD is unclear.7 MRI markers of CVD-white matter hyperintensities (WMH), brain infarcts (BI), and cerebral microbleeds (CMB)-are powerful predictors of stroke and dementia.10-13 They are highly prevalent in older community-dwelling persons, [14][15][16] and can be assessed noninvasively and quantitatively in large population-based samples. Dissecting the relationship between APOE and MRI

APOE/TOMM40 Genetic Loci, White Matter Hyperintensities, and Cerebral Microbleeds

“…In terms of CMB, this report does not align with recent meta‐analyses that concluded significant deleterious effects of APOE ε4 6, 7. Of those meta‐analyses, Schilling et al .…”

“…5 did not stratify analyses by whether participants were generally healthy or not (total n  = 8546), whereas Schilling et al . 6 did (‘healthy’ n  = 8405). However, these reports were not independent because some common data were included in both.…”

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

“…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.…”

“…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. 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.…”

“…24 However, APOE ε2 allele carrier status was associated with white matter hyperintensity and the risk of brain infarcts. 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.…”