Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Alzheimer Neurobiology Center, Stockholm, Sweden.
Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, Center of Neurology, University of Tuebingen, Tuebingen, Germany; DZNE, German Center for Neurodegenerative Diseases, Tuebingen, Tuebingen, Germany.
Alzheimers Dement. 2014 Sep;10(5):530-540.e1. doi: 10.1016/j.jalz.2013.03.010. Epub 2013 Aug 24.
Apolipoprotein E ε4 allele (APOE ε4) increases the apolipoprotein E (apoE) protein levels in Alzheimer's disease (AD) cerebrospinal fluid (CSF). Thus, we hypothesized that apoE levels were also associated with the APOE genotype, and amyloid-β (Aβ)-associated clinical, functional, and imaging parameters in patients with Lewy body-associated disorders (LBD). Indeed, similar to AD, patients with LBD displayed high CSF apoE levels (greatest in patients with dementia with LBD), and this was linked to APOE ε4. High CSF apoE protein correlated positively with CSF soluble amyloid precursor protein, total tau, and cortical and striatal Pittsburgh compound B retention; and correlated negatively with CSF Aβ42, cognitive tests scores, and glucose uptake ratio in the temporal and parietal cortices. APOE ε4-triggered accumulation of apoE in CSF is related to Aβ-associated clinical and functional imaging parameters in LBD. Accordingly, therapeutic strategies aimed at reducing apoE levels in the brain should be explored not only in AD but also in LBD, particularly when accompanied with dementia.
载脂蛋白 E ε4 等位基因 (APOE ε4) 增加了阿尔茨海默病 (AD) 脑脊液 (CSF) 中的载脂蛋白 E (apoE) 蛋白水平。因此，我们假设 apoE 水平也与 APOE 基因型以及路易体相关疾病 (LBD) 患者的淀粉样蛋白-β (Aβ) 相关的临床、功能和影像学参数有关。事实上，与 AD 相似，LBD 患者的 CSF apoE 水平较高（以痴呆伴 LBD 患者最高），这与 APOE ε4 有关。高 CSF apoE 蛋白与 CSF 可溶性淀粉样前体蛋白、总 tau 以及皮质和纹状体匹兹堡化合物 B 保留呈正相关；与 CSF Aβ42、认知测试评分和颞叶和顶叶皮质的葡萄糖摄取率呈负相关。APOE ε4 触发的 apoE 在 CSF 中的积累与 LBD 中的 Aβ 相关的临床和功能影像学参数有关。因此，不仅在 AD 中，而且在 LBD 中，特别是当伴有痴呆时，应该探索旨在降低大脑中 apoE 水平的治疗策略。
