■血脑屏障(BBB)的破坏被认为是痴呆的潜在机制。阿尔茨海默病(AD)生物标志物和血管因子也与BBB通透性相关。
■在本研究中,研究了AD的神经病理学生物标志物和BBB的慢性血管危险因素的联合作用.
■脑脊液(CSF)/血清白蛋白比(Qalb),BBB渗透性的指标,在总共95名住院痴呆症患者中进行了测量。人口统计,临床信息,和实验室检查是从住院记录中收集的。还收集了AD和载脂蛋白E(APOE)基因型的CSF神经病理学生物标志物。中介分析模型用于计算AD(介体)的神经病理学生物标志物之间的关联,Qalb,和慢性血管危险因素。
■三种类型的痴呆症,AD(n=52),路易体痴呆(LBD,n=19),额颞叶变性(n=24),包括平均Qalb为7.18(±4.36)。Qalb在2型糖尿病痴呆患者中显著升高(T2DM,p=0.004),但基于APOEε4等位基因的存在没有差异,CMBs,或淀粉样蛋白/tau/神经变性(ATN)框架。Qalb与Aβ1-42(B=-20.775,p=0.009)和Aβ1-40(B=-305.417,p=0.005)水平呈负相关,与T2DM(B=3.382,p<0.001)和糖基化血红蛋白(GHb,B=1.163,p<0.001)和空腹血糖(FBG,B=1.443,p<0.001)。GHb是较高Qalb的直接慢性血管危险因素(总效应B=1.135,95%CI:0.611-1.659,p<0.001)。Aβ1-42/Aβ1-40或t-tau/Aβ1-42的比率是Qalb和GHb之间关联的介质;GHb对Qalb的直接作用为1.178(95%CI:0.662-1.694,p<0.001)。
■葡萄糖暴露可以通过Aβ和tau直接或间接影响BBB完整性,提示葡萄糖影响BBB分解,葡萄糖稳定性在痴呆保护和治疗中起重要作用.
UNASSIGNED: Blood brain barrier (BBB) breakdown is considered a potential mechanism of dementia. The Alzheimer\'s disease (AD) biomarkers and vascular factors are also associated with BBB permeability.
UNASSIGNED: In the present study, the combination effects of neuropathological biomarkers of AD and chronic vascular risk factors for BBB were investigated.
UNASSIGNED: The cerebrospinal fluid (CSF)/serum albumin ratio (
Qalb), an indicator of BBB permeability, was measured in a total of 95 hospitalized dementia patients. The demographics, clinical information, and laboratory tests were collected from the inpatient records. The CSF neuropathological biomarkers of AD and apolipoprotein E (APOE) genotype were also collected. The mediation analysis model was used to calculate the associations among neuropathological biomarkers of AD (mediator), the
Qalb, and chronic vascular risk factors.
UNASSIGNED: Three types of dementia, AD (n = 52), Lewy body dementia (LBD, n = 19), and frontotemporal lobar degeneration (n = 24), were included with a mean Qalb of 7.18 (± 4.36). The
Qalb was significantly higher in dementia patients with type 2 diabetes mellitus (T2DM, p = 0.004) but did not differ based on the presence of APOE ε4 allele, CMBs, or amyloid/tau/neurodegeneration (ATN) framework. The
Qalb was negatively associated with the levels of Aβ1-42 (B = -20.775, p = 0.009) and Aβ1-40 (B = -305.417, p = 0.005) and positively associated with the presence of T2DM (B = 3.382, p < 0.001) and the levels of glycosylated hemoglobin (GHb, B = 1.163, p < 0.001) and fasting blood glucose (FBG, B = 1.443, p < 0.001). GHb is a direct chronic vascular risk factor for higher Qalb (total effect B = 1.135, 95% CI: 0.611-1.659, p < 0.001). Ratios of Aβ1-42/Aβ1-40 or t-tau/Aβ1-42 were mediators of the association between the Qalb and GHb; the direct effect of GHb on the
Qalb was 1.178 (95% CI: 0.662-1.694, p < 0.001).
UNASSIGNED: Glucose exposure can directly or indirectly affect BBB integrity through Aβ and tau, indicating glucose affects BBB breakdown and glucose stability plays an important role in dementia protection and management.