Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, New York 10016, USA.
Biol Psychiatry. 2010 Nov 15;68(10):913-21. doi: 10.1016/j.biopsych.2010.07.011.
Epidemiology and imaging studies showed that cognitively normal (NL) individuals with a maternal history (MH) of late-onset Alzheimer's disease (LOAD) might be at increased risk for Alzheimer's disease (AD) compared with NL with a paternal history (PH) and NL with a negative family history of LOAD (NH). With a panel of cerebrospinal fluid (CSF) markers, this study examined whether NL MH showed evidence for AD pathology compared with PH and NH.
Fifty-nine 40-80-year-old NL subjects were examined, including 23 MH and 14 PH whose parents had a clinician-certified diagnosis of LOAD and 22 NH. All subjects completed clinical neuropsychological examinations and a lumbar puncture to measure CSF levels of amyloid-beta (Aβ(40), Aβ(42), Aβ(42/40)), total and hyperphosphorylated tau (T-Tau and P-Tau(231); markers of axonal degeneration and neurofibrillary tangles, respectively), and F₂-isoprostanes (IsoP) (a marker of oxidative stress).
Groups were comparable for demographic and neuropsychological measures. The MH subjects showed higher IsoP and reduced Aβ(42/40) CSF levels compared with NH and with PH (p values ≤ .05), whereas no differences were found between NH and PH. No group differences were found for P-Tau(231) and T-Tau. The IsoP and Aβ(42/40) levels were correlated only within the MH group (R² = .32, p = .005) and discriminated MH from the other subjects with 70% accuracy (relative risk = 3.7%, 95% confidence interval = 1.6-9.7, p < .001). Results remained significant controlling for age, gender, education, and apolipoprotein E genotype.
Adult children of LOAD-affected mothers express a pathobiological phenotype characterized by Aβ-associated oxidative stress consistent with AD, which might reflect increased risk for developing the disease.
流行病学和影像学研究表明，与有父系家族史（PH）和无 LOAD 家族史（NH）的认知正常（NL）个体相比，有 LOAD 母系家族史（MH）的 NL 个体发生阿尔茨海默病（AD）的风险可能增加。本研究采用一组脑脊液（CSF）标志物，旨在探讨 NL MH 是否与 PH 和 NH 相比存在 AD 病理证据。
共纳入 59 名 40-80 岁 NL 受试者，其中 23 名 MH、14 名 PH，其父母均经临床医生确诊为 LOAD，22 名 NH。所有受试者均完成了临床神经心理学检查和腰椎穿刺，以测量 CSF 中淀粉样β（Aβ（40）、Aβ（42）、Aβ（42/40））、总 tau（T-Tau）和磷酸化 tau（P-Tau（231））（分别为轴突退变和神经原纤维缠结的标志物）和 F₂-异前列腺素（IsoP）（氧化应激标志物）的水平。
各组在人口统计学和神经心理学指标方面无差异。与 NH 和 PH 相比，MH 受试者的 IsoP 水平较高，Aβ（42/40）CSF 水平较低（p 值均≤.05），而 NH 和 PH 之间无差异。各组之间 P-Tau（231）和 T-Tau 水平无差异。仅在 MH 组中，IsoP 和 Aβ（42/40）水平之间存在相关性（R² =.32，p =.005），且 IsoP 和 Aβ（42/40）可将 MH 与其他受试者区分开来，其准确率为 70%（相对风险 = 3.7%，95%置信区间 = 1.6-9.7，p <.001）。在校正年龄、性别、教育程度和载脂蛋白 E 基因型后，结果仍有统计学意义。
LOAD 患者的成年子女表现出一种以 Aβ 相关氧化应激为特征的病理表型，这与 AD 一致，这可能反映出他们发生该病的风险增加。
