Janelidze Shorena, Hertze Joakim, Nägga Katarina, Nilsson Karin, Nilsson Christer, Wennström Malin, van Westen Danielle, Blennow Kaj, Zetterberg Henrik, Hansson Oskar
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden.
Neurobiol Aging. 2017 Mar;51:104-112. doi: 10.1016/j.neurobiolaging.2016.11.017. Epub 2016 Dec 5.
Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls. However, this measure was not changed during preclinical or prodromal Alzheimer's disease and was not associated with amyloid positron emission tomography or APOE genotype. The Qalb was increased in diabetes mellitus and correlated positively with CSF biomarkers of angiogenesis and endothelial dysfunction (vascular endothelial growth factor, intracellular adhesion molecule 1, and vascular cell adhesion molecule 1). In healthy elderly, high body mass index and waist-hip ratio predicted increased Qalb 20 years later. In summary, BBB permeability is increased in major dementia disorders but does not relate to amyloid pathology or APOE genotype. Instead, BBB impairment may be associated with diabetes and brain microvascular damage.
血脑屏障（BBB）功能障碍可能是许多神经退行性疾病的一个重要组成部分。在本研究中，我们使用大型临床队列研究了其在痴呆症中的作用。共对1015名个体测量了脑脊液（CSF）/血浆白蛋白比率（Qalb），这是BBB（以及血脑脊液屏障）通透性的一个指标。与对照组相比，阿尔茨海默病、路易体痴呆或帕金森病痴呆、皮质下血管性痴呆和额颞叶痴呆患者的该比率升高。然而，在临床前或前驱期阿尔茨海默病期间，这一指标没有变化，并且与淀粉样蛋白正电子发射断层扫描或APOE基因型无关。糖尿病患者的Qalb升高，并且与血管生成和内皮功能障碍的CSF生物标志物（血管内皮生长因子、细胞间黏附分子1和血管细胞黏附分子1）呈正相关。在健康老年人中，高体重指数和腰臀比预示20年后Qalb会升高。总之，主要痴呆症疾病中BBB通透性增加，但与淀粉样蛋白病理学或APOE基因型无关。相反，BBB损伤可能与糖尿病和脑微血管损伤有关。
