Jochemsen Hadassa M, van der Flier Wiesje M, Ashby Emma L, Teunissen Charlotte E, Jones Ruth E, Wattjes Mike P, Scheltens Philip, Geerlings Mirjam I, Kehoe Patrick G, Muller Majon
Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
J Alzheimers Dis. 2015;44(1):153-62. doi: 10.3233/JAD-131496.
Higher angiotensin-converting enzyme (ACE) activity might increase the risk of Alzheimer's disease by increasing blood pressure, and subsequent development of cerebral small vessel disease (CSVD). Yet, it may also decrease this risk, as it functions to degrade amyloid-β, thereby reducing brain atrophy.
To examine the cross-sectional associations of serum and cerebrospinal fluid (CSF) ACE protein levels and activity with brain atrophy and CSVD in a memory clinic cohort.
In 118 subjects from the memory clinic based Amsterdam Dementia Cohort (mean age 66 ± 8 years), ACE protein levels (ng/ml) and activity in CSF and serum were investigated. Poisson regression analyses were used to associate ACE measurements with rated global cortical atrophy, medial temporal lobe atrophy, lacunar infarcts, white matter hyperintensities, and microbleeds on brain MRI.
Higher CSF ACE activity was associated with a reduced risk of global brain atrophy. The relative risk (95% CI) of having global cortical atrophy ≥2 per SD increase in CSF ACE activity was 0.67 (0.49; 0.93). ACE levels were not significantly related to measures of CSVD.
These results show that high ACE might have protective effects on the brain. This could suggest that ACE inhibitors, which may lower CSF ACE levels, are not preferred as antihypertensive treatment in patients at risk for Alzheimer's disease.
较高的血管紧张素转换酶（ACE）活性可能通过升高血压以及随后引发脑小血管疾病（CSVD）而增加患阿尔茨海默病的风险。然而，它也可能降低这种风险，因为其作用是降解淀粉样β蛋白，从而减少脑萎缩。
在一个记忆门诊队列中研究血清和脑脊液（CSF）ACE蛋白水平及活性与脑萎缩和CSVD的横断面关联。
在来自基于阿姆斯特丹痴呆队列的记忆门诊的118名受试者（平均年龄66±8岁）中，研究了CSF和血清中的ACE蛋白水平（ng/ml）及活性。采用泊松回归分析将ACE测量值与脑MRI上的整体皮质萎缩、内侧颞叶萎缩、腔隙性梗死、白质高信号和微出血进行关联。
较高的CSF ACE活性与全球脑萎缩风险降低相关。CSF ACE活性每增加1个标准差，发生全球皮质萎缩≥2级的相对风险（95%CI）为0.67（0.49；0.93）。ACE水平与CSVD测量指标无显著相关性。
这些结果表明，高ACE可能对大脑有保护作用。这可能意味着，可能会降低CSF ACE水平的ACE抑制剂，并非有患阿尔茨海默病风险患者的首选降压治疗药物。
