Chongqing Three Gorges Medical College, Chongqing, China.
General Medical Wards, The Affiliated Children's Hospital of Chongqing Medical University, Chongqing, China.
Eur Neurol. 2021;84(6):472-480. doi: 10.1159/000516774. Epub 2021 Aug 2.
Apolipoprotein E (APOE) ε4 is highly associated with mild cognitive impairment (MCI). However, the specific influence of APOE ε4 status on tau pathology and cognitive decline in early MCI (EMCI) and late MCI (LMCI) is poorly understood. Our goal was to evaluate the association of APOE ε4 with cerebrospinal fluid (CSF) tau levels and cognition in EMCI and LMCI patients in the Alzheimer's Disease Neuroimaging Initiative database, and whether this association was mediated by amyloid-β (Aβ).
Participants were 269 cognitively normal (CN), 262 EMCI, and 344 LMCI patients. They underwent CSF Aβ42 and tau detection, APOE ε4 genotyping, Mini-Mental State Examination, (MMSE), and Alzheimer's disease assessment scale (ADAS)-cog assessments. Linear regressions were used to examine the relation of APOE ε4 and CSF tau levels and cognitive scores in persons with and without Aβ deposition (Aβ+ and Aβ-).
The prevalence of APOE ε4 is higher in EMCI and LMCI than in CN (p < 0.001 for both), and in LMCI than in EMCI (p = 0.001). APOE ε4 allele was significantly higher in Aβ+ subjects than in Aβ- subjects (p < 0.001). Subjects who had a lower CSF Aβ42 level and were APOE ε4-positive experienced higher levels of CSF tau and cognitive scores in EMCI and/or LMCI.
An APOE ε4 allele is associated with increased CSF tau and worse cognition in both EMCI and LMCI, and this association may be mediated by Aβ. We conclude that APOE ε4 may be an important mediator of tau pathology and cognition in the early stages of AD.
载脂蛋白 E (APOE) ε4 与轻度认知障碍 (MCI) 高度相关。然而，APOE ε4 状态对早期 MCI (EMCI) 和晚期 MCI (LMCI) 中 tau 病理学和认知下降的具体影响知之甚少。我们的目标是评估 APOE ε4 与阿尔茨海默病神经影像学倡议 (Alzheimer's Disease Neuroimaging Initiative, ADNI) 数据库中 EMCI 和 LMCI 患者的脑脊液 (CSF) tau 水平和认知的关系，以及这种关系是否由淀粉样蛋白-β (amyloid-β, Aβ) 介导。
参与者包括 269 名认知正常 (cognitively normal, CN)、262 名 EMCI 和 344 名 LMCI 患者。他们接受了 CSF Aβ42 和 tau 检测、APOE ε4 基因分型、简易精神状态检查 (Mini-Mental State Examination, MMSE) 和阿尔茨海默病评估量表 (Alzheimer's disease assessment scale, ADAS)-cog 评估。线性回归用于检查 APOE ε4 与 CSF tau 水平和有或无 Aβ 沉积 (Aβ+ 和 Aβ-) 的个体认知评分之间的关系。
EMCI 和 LMCI 中 APOE ε4 的患病率高于 CN (两者均 p < 0.001)，而 LMCI 中 APOE ε4 的患病率高于 EMCI (p = 0.001)。APOE ε4 等位基因在 Aβ+ 受试者中显著高于 Aβ- 受试者 (p < 0.001)。CSF Aβ42 水平较低且 APOE ε4 阳性的受试者在 EMCI 和/或 LMCI 中表现出更高的 CSF tau 和认知评分。
APOE ε4 等位基因与 EMCI 和 LMCI 中 CSF tau 增加和认知下降有关，这种关联可能由 Aβ 介导。我们得出结论，APOE ε4 可能是 AD 早期 tau 病理学和认知的重要介导物。
