From the Veterans Affairs San Diego Healthcare System (D.A.N., M.W.B., L.D.-W.), San Diego; Departments of Neurosciences (S.D.E., D.P.S., D.R.G.) and Psychiatry (M.W.B., L.D.-W.), University of California, San Diego, La Jolla, CA; VA Puget Sound Health Care System (E.R.P.), Mental Illness Research, Education, and Clinical Center, Seattle; Departments of Psychiatry and Behavioral Sciences (E.R.P.), University of Washington School of Medicine, Seattle, WA; Department of Neurology (J.F.Q.), Oregon Health and Science University, Portland; and Portland VA Medical Center (J.F.Q.), Portland, OR.
Neurology. 2013 Dec 3;81(23):2024-7. doi: 10.1212/01.wnl.0000436935.47657.78. Epub 2013 Nov 13.
The current study examined the association between pulse pressure (PP) and CSF-based biomarkers for Alzheimer disease, including β-amyloid 1-42 (Aβ1-42) and phosphorylated tau (P-tau) protein, in cognitively normal older adults.
One hundred seventy-seven cognitively normal, stroke-free older adult participants (aged 55-100 years) underwent blood pressure assessment for determination of PP (systolic - diastolic blood pressure) and lumbar puncture for measurement of CSF Aβ1-42 and P-tau. Pearson correlations and multiple linear regression, controlling for age, sex, APOE genotype, and body mass index, evaluated the relationship between PP and Alzheimer disease biomarkers.
PP elevation was associated with increased P-tau (r = 0.23, p = 0.002), reduced Aβ1-42 (r = -0.19, p = 0.01), and increased P-tau to Aβ1-42 ratio (r = 0.27, p < 0.001). After controlling for covariates, PP remained associated with P-tau (β = 0.18, p = 0.0196) and P-tau to Aβ1-42 ratio (β = 0.0016, p < 0.001) but was no longer associated with Aβ1-42 (β = -0.1, p = 0.35). Post hoc multivariate analyses indicated that increased PP was associated with all biomarkers in younger participants (aged 55-70 years) (Aβ1-42: p = 0.050; P-tau: p = 0.003; P-tau to Aβ ratio: p = 0.0007) but not older participants (aged 70-100 years).
PP elevation is associated with increased CSF P-tau and decreased Aβ1-42 in cognitively normal older adults, suggesting that pulsatile hemodynamics may be related to amyloidosis and tau-related neurodegeneration. The relationship between PP and CSF biomarkers is age-dependent and observed only in participants in the fifth and sixth decades of life.
本研究旨在探讨脉压（PP）与阿尔茨海默病的脑脊液生物标志物之间的关系，包括β-淀粉样蛋白 1-42（Aβ1-42）和磷酸化 tau 蛋白（P-tau），在认知正常的老年人中。
177 名认知正常、无中风的老年参与者（年龄 55-100 岁）接受血压评估以确定 PP（收缩压-舒张压），并进行腰椎穿刺以测量脑脊液 Aβ1-42 和 P-tau。采用 Pearson 相关分析和多元线性回归分析，控制年龄、性别、APOE 基因型和体重指数，评估 PP 与阿尔茨海默病生物标志物之间的关系。
PP 升高与 P-tau 升高（r = 0.23，p = 0.002）、Aβ1-42 降低（r = -0.19，p = 0.01）和 P-tau 与 Aβ1-42 比值升高（r = 0.27，p <0.001）相关。在控制了混杂因素后，PP 仍然与 P-tau（β = 0.18，p = 0.0196）和 P-tau 与 Aβ1-42 比值（β = 0.0016，p <0.001）相关，但与 Aβ1-42 不相关（β = -0.1，p = 0.35）。事后多元分析表明，在较年轻的参与者（55-70 岁）中，PP 升高与所有生物标志物均相关（Aβ1-42：p = 0.050；P-tau：p = 0.003；P-tau 与 Aβ 比值：p = 0.0007），但在年龄较大的参与者（70-100 岁）中不相关。
PP 升高与认知正常的老年人脑脊液中 P-tau 升高和 Aβ1-42 降低相关，提示脉动血流动力学可能与淀粉样蛋白沉积和 tau 相关的神经退行性变有关。PP 与 CSF 生物标志物之间的关系具有年龄依赖性，仅在 50 至 60 岁的参与者中观察到。
