Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston, MA, USA.
J Alzheimers Dis. 2020;78(3):1229-1236. doi: 10.3233/JAD-200656.
Brain metal homeostasis is essential for brain health, and deregulation can result in oxidative stress on the brain parenchyma.
Our objective in this study was to focus on two hemorrhagic MRI manifestations of small vessel disease [cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS)] and associations with cerebrospinal fluid (CSF) iron levels. In addition, we aimed to analyze CSF biomarkers for dementia and associations with CSF metal levels.
This is a cross-sectional study of 196 patients who underwent memory clinic investigation, including brain MRI. CSF was collected and analyzed for metals, amyloid-β (Aβ) 42, total tau (T-tau), and phosphorylated tau (P-tau), and CSF/serum albumin ratios. Statistical analyses were performed using generalized linear models.
No significant difference was found between CSF metal levels across diagnostic groups. Higher iron and copper levels were associated with higher CSF levels of Aβ42, T-tau, P-tau, and CSF/serum albumin ratios (p < 0.05). Zinc was associated with higher CSF/serum albumin ratios. There was no significant association between CMBs or cSS and CSF iron levels. An increase in CSF iron with the number of CMBs was seen in APOEɛ4 carriers.
CSF iron levels are elevated with cerebral microbleeds in APOEɛ4 carriers, with no other association seen with hemorrhagic markers of small vessel disease. The association of elevated CSF iron and copper with tau could represent findings of increased neurodegeneration in these patients.
脑内金属稳态对大脑健康至关重要，其失调可导致脑实质氧化应激。
本研究旨在关注小血管疾病的两种出血性 MRI 表现[脑微出血（CMB）和皮质浅表铁沉积症（cSS）]及其与脑脊液（CSF）铁水平的关系。此外，我们旨在分析与 CSF 金属水平相关的 CSF 生物标志物。
这是一项对 196 名接受记忆诊所检查（包括脑 MRI）的患者进行的横断面研究。采集 CSF 并分析金属、淀粉样蛋白-β（Aβ42）、总 tau（T-tau）、磷酸化 tau（P-tau）和 CSF/血清白蛋白比值。使用广义线性模型进行统计分析。
不同诊断组之间 CSF 金属水平无显著差异。较高的铁和铜水平与较高的 CSF Aβ42、T-tau、P-tau 和 CSF/血清白蛋白比值相关（p<0.05）。锌与较高的 CSF/血清白蛋白比值相关。CMB 或 cSS 与 CSF 铁水平之间无显著相关性。在 APOEɛ4 携带者中，CSF 铁水平随 CMB 数量的增加而升高。
APOEɛ4 携带者的 CSF 铁水平与脑微出血有关，与小血管疾病的其他出血性标志物无其他关联。CSF 铁和铜升高与 tau 的关联可能代表这些患者神经退行性变增加的发现。
