The relation between APOE genotype and cerebral microbleeds in cognitively unimpaired middle- and old-aged individuals,Neurobiology of Aging

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The relation between APOE genotype and cerebral microbleeds in cognitively unimpaired middle- and old-aged individuals
Neurobiology of Aging ( IF 3.7 ) Pub Date : 2020-11-01 , DOI: 10.1016/j.neurobiolaging.2020.06.015
Silvia Ingala ₁ , Linda Mazzai ₂ , Carole H Sudre ₃ , Gemma Salvadó ₄ , Anna Brugulat-Serrat ₅ , Viktor Wottschel ₁ , Carles Falcon ₄ , Grégory Operto ₆ , Betty Tijms ₇ , Juan Domingo Gispert ₈ , José Luis Molinuevo ₉ , Frederik Barkhof ₁₀ ,

Affiliation

Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands; Department of Medicine (DiMED), Institute of Radiology, University of Padua, Padua, Italy.
Engineering and Imaging Sciences, King's College London, London, UK; Dementia Research Centre, University College London, London, UK; Centre for Medical Imaging Computing, Faculty of Engineering, University College London, London, UK.
Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Pompeu Fabra University, Barcelona, Spain.
Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain; Pompeu Fabra University, Barcelona, Spain.
Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Pompeu Fabra University, Barcelona, Spain; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain.
Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands; Institutes of Neurology and Healthcare Engineering, UCL, London, UK.

Positive associations between cerebral microbleeds (CMBs) and APOE-ε4 (apolipoprotein E) genotype have been reported in Alzheimer's disease, but show conflicting results. We investigated the effect of APOE genotype on CMBs in a cohort of cognitively unimpaired middle- and old-aged individuals enriched for APOE-ε4 genotype. Participants from ALFA (Alzheimer and Families) cohort were included and their magnetic resonance scans assessed (n = 564, 50% APOE-ε4 carriers). Quantitative magnetic resonance analyses included visual ratings, atrophy measures, and white matter hyperintensity (WMH) segmentations. The prevalence of CMBs was 17%, increased with age (p < 0.05), and followed an increasing trend paralleling APOE-ε4 dose. The number of CMBs was significantly higher in APOE-ε4 homozygotes compared to heterozygotes and non-carriers (p < 0.05). This association was driven by lobar CMBs (p < 0.05). CMBs co-localized with WMH (p < 0.05). No associations between CMBs and APOE-ε2, gray matter volumes, and cognitive performance were found. Our results suggest that cerebral vessels of APOE-ε4 homozygous are more fragile, especially in lobar locations. Co-occurrence of CMBs and WMH suggests that such changes localize in areas with increased vascular vulnerability.

中文翻译：

APOE基因型与认知未受损中老年人脑微出血的关系

脑微出血 (CMB) 和 APOE-ε4（载脂蛋白 E）基因型在阿尔茨海默病中呈正相关，但结果相互矛盾。我们研究了 APOE 基因型对一组富含 APOE-ε4 基因型的认知未受损中老年人群中 CMB 的影响。包括来自 ALFA（阿尔茨海默病和家庭）队列的参与者并评估了他们的磁共振扫描（n = 564，50% APOE-ε4 携带者）。定量磁共振分析包括视觉评级、萎缩措施和白质高信号 (WMH) 分割。CMB 的患病率为 17%，随着年龄的增长而增加（p < 0.05），并且随着 APOE-ε4 剂量的增加而增加。与杂合子和非携带者相比，APOE-ε4 纯合子中 CMB 的数量显着更高（p < 0. 05）。这种关联是由大叶 CMB 驱动的（p < 0.05）。CMB 与 WMH 共定位（p < 0.05）。未发现 CMB 与 APOE-ε2、灰质体积和认知能力之间存在关联。我们的结果表明 APOE-ε4 纯合子的脑血管更脆弱，尤其是在脑叶位置。CMBs 和 WMH 的同时发生表明这种变化发生在血管脆弱性增加的区域。

更新日期：2020-11-01

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