<i>APOE</i>
            ε4 is associated with younger age at ischemic stroke onset but not with stroke outcome

Lagging, Cecilia; Lorentzen, Erik; Stanne, Tara M.; Pedersén, Annie; Söderholm, Martin; Cole, John W.; Jood, Katarina; Lemmens, Robin; Phuah, Chia-Ling; Rost, Natalia S.; Thijs, Vincent; Woo, Daniel; Maguire, Jane; Lindgren, Arne; Jern, Christina

doi:10.1212/wnl.0000000000008459

Cited by 20 publications

(21 citation statements)

References 10 publications

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“…When endophenotypes, such as stroke subtypes, are taken into account to assess allelic risk, the same pattern is observed, where ε2 promotes hemorrhages and ε4 promotes amyloid-β accumulation ( Sudlow et al, 2006 ). Some have suggested that the ε4 allele is only associated with an earlier onset of disease and not with disease severity both in CAA and stroke ( Greenberg et al, 1996 ; Lagging et al, 2019 ).…”

Section: Genetics Of Vascular Dementiamentioning

confidence: 99%

Genetic architecture of common non-Alzheimer’s disease dementias

Guerreiro

Gibbons

Tábuas‐Pereira

et al. 2020

Neurobiology of Disease

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Frontotemporal dementia (FTD), dementia with Lewy bodies (DLB) and vascular dementia (VaD) are the most common forms of dementia after Alzheimer’s disease (AD). The heterogeneity of these disorders and/or the clinical overlap with other diseases hinder the study of their genetic components. Even though Mendelian dementias are rare, the study of these forms of disease can have a significant impact in the lives of patients and families and have successfully brought to the fore many of the genes currently known to be involved in FTD and VaD, starting to give us a glimpse of the molecular mechanisms underlying these phenotypes. More recently, genome-wide association studies have also pointed to disease risk-associated loci. This has been particularly important for DLB where familial forms of disease are very rarely described. In this review we systematically describe the Mendelian and risk genes involved in these non-AD dementias in an effort to contribute to a better understanding of their genetic architecture, find differences and commonalities between different dementia phenotypes, and uncover areas that would benefit from more intense research endeavors.

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Section: Genetics Of Vascular Dementiamentioning

confidence: 99%

Genetic architecture of common non-Alzheimer’s disease dementias

Guerreiro

Gibbons

Tábuas‐Pereira

et al. 2020

Neurobiology of Disease

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“…This finding is consistent with a meta-analysis that found ApoE ε4 polymorphism to be associated with younger age at ischemic stroke onset. 42 The biology underlying this association in patients with stroke is uncertain, but might overlap with effects of this polymorphism in the setting of Alzheimer’s disease, where a single ApoE ε4 allele is associated with dementia age of onset that is 3.1 43 –8.8 44 years younger.…”

Section: Discussionmentioning

confidence: 99%

Genetic Factors, Brain Atrophy, and Response to Rehabilitation Therapy After Stroke

Cramer

See

Liu

et al. 2021

Neurorehabil Neural Repair

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Objective Patients show substantial differences in response to rehabilitation therapy after stroke. We hypothesized that specific genetic profiles might explain some of this variance and, secondarily, that genetic factors are related to cerebral atrophy post-stroke. Methods The phase 3 ICARE study examined response to motor rehabilitation therapies. In 216 ICARE enrollees, DNA was analyzed for presence of the BDNF val66met and the ApoE ε4 polymorphism. The relationship of polymorphism status to 12-month change in motor status (Wolf Motor Function Test, WMFT) was examined. Neuroimaging data were also evaluated (n=127). Results Subjects were 61±13 years old (mean±SD) and enrolled 43±22 days post-stroke; 19.7% were BDNF val66met carriers and 29.8% ApoE ε4 carriers. Carrier status for each polymorphism was not associated with WMFT, either at baseline or over 12 months of follow-up. Neuroimaging, acquired 5±11 days post-stroke, showed that BDNF val66met polymorphism carriers had a 1.34-greater degree of cerebral atrophy compared to non-carriers (P=.01). Post hoc analysis found that age of stroke onset was 4.6 years younger in subjects with the ApoE ε4 polymorphism (P=.02). Conclusion Neither the val66met BDNF nor ApoE ε4 polymorphism explained inter-subject differences in response to rehabilitation therapy. The BDNF val66met polymorphism was associated with cerebral atrophy at baseline, echoing findings in healthy subjects, and suggesting an endophenotype. The ApoE ε4 polymorphism was associated with younger age at stroke onset, echoing findings in Alzheimer’s disease and suggesting a common biology. Genetic associations provide insights useful to understanding the biology of outcomes after stroke.

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“…APOE-ε4, in particular, has been associated with late-onset AD [ 44 - 46 ]. Furthermore, several cardiovascular and neurological diseases have shown the involvement of APOE [ 47 - 50 ]. The different APOE confer variable risks to AD.…”

Section: Apolipoprotein E: Function and Role In Admentioning

confidence: 99%

Alzheimer Disease: Recent Updates on Apolipoprotein E and Gut Microbiome Mediation of Oxidative Stress, and Prospective Interventional Agents

Botchway¹,

Okoye²,

Chen³

et al. 2022

Aging and disease

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Alzheimer’s disease (AD) is a current public health challenge and will remain until the development of an effective intervention. However, developing an effective treatment for the disease requires a thorough understanding of its etiology, which is currently lacking. Although several studies have shown the association between oxidative damage and AD, only a few have clarified the specific mechanisms involved. Herein, we reviewed recent preclinical and clinical studies that indicated the significance of oxidative damage in AD, as well as potential antioxidants. Although several factors regulate oxidative stress in AD, we centered our investigation on apolipoprotein E and the gut microbiome. Apolipoprotein E, particularly apolipoprotein E-ε4, can impair the structural facets of the mitochondria. This, in turn, can minimize the mitochondrial functionality and result in the progressive build-up of free radicals, eventually leading to oxidative stress. Similarly, the gut microbiome can influence oxidative stress to a significant degree via its metabolite, trimethylamine N-oxide. Given the various roles of these two factors in modulating oxidative stress, we also discuss the possible relationship between them and provide future research directions.

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APOE ε4 is associated with younger age at ischemic stroke onset but not with stroke outcome

Cited by 20 publications

References 10 publications

Genetic architecture of common non-Alzheimer’s disease dementias

Genetic architecture of common non-Alzheimer’s disease dementias

Genetic Factors, Brain Atrophy, and Response to Rehabilitation Therapy After Stroke

Alzheimer Disease: Recent Updates on Apolipoprotein E and Gut Microbiome Mediation of Oxidative Stress, and Prospective Interventional Agents

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