在纵向随访的轻度认知障碍和阿尔茨海默病患者中，血浆载脂蛋白 E 水平。

Plasma apolipoprotein E levels in longitudinally followed patients with mild cognitive impairment and Alzheimer's disease.

机构信息

Department of Biochemistry and Biophysics, Stockholm University, Svante Arrhenius Väg 16B, 106 91, Stockholm, Sweden.

Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.

出版信息

Alzheimers Res Ther. 2022 Aug 24;14(1):115. doi: 10.1186/s13195-022-01058-9.

DOI:10.1186/s13195-022-01058-9

PMID:36002891

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9400269/

Abstract

BACKGROUND

Low levels of plasma apolipoprotein E (apoE) and presence of the APOE ε4 allele are associated with an increased risk of Alzheimer's disease (AD). Although the increased risk of AD in APOE ε4-carriers is well-established, the protein levels have received limited attention.

METHODS

We here report the total plasma apoE and apoE isoform levels at baseline from a longitudinally (24 months) followed cohort including controls (n = 39), patients with stable amnestic mild cognitive impairment during 24 months follow up (MCI-MCI, n = 30), patients with amnestic MCI (aMCI) that during follow-up were clinically diagnosed with AD with dementia (ADD) (MCI-ADD, n = 28), and patients with AD with dementia (ADD) at baseline (ADD, n = 28). We furthermore assessed associations between plasma apoE levels with cerebrospinal fluid (CSF) AD biomarkers and α-synuclein, as well as both CSF and plasma neurofilament light chain (NfL), YKL-40 and kallikrein 6.

RESULTS

Irrespective of clinical diagnosis, the highest versus the lowest apoE levels were found in APOE ε2/ε3 versus APOE ε4/ε4 subjects, with the most prominent differences exhibited in females. Total plasma apoE levels were 32% and 21% higher in the controls versus MCI-ADD and ADD patients, respectively. Interestingly, MCI-ADD patients exhibited a 30% reduction in plasma apoE compared to MCI-MCI patients. This decrease appeared to be associated with brain amyloid-β (Aβ) pathology regardless of disease status as assessed using the Amyloid, Tau, and Neurodegeneration (A/T/N) classification. In addition to the association between low plasma apoE and low levels of CSF Aβ, lower apoE levels were also related to higher levels of CSF total tau (t-tau) and tau phosphorylated at Threonine 181 residue (p-tau) and NfL as well as a worse performance on the mini-mental-state-examination. In MCI-ADD patients, low levels of plasma apoE were associated with higher levels of CSF α-synuclein and kallikrein 6. No significant correlations between plasma apoE and the astrocytic inflammatory marker YKL40 were observed.

CONCLUSIONS

Our results demonstrate important associations between low plasma apoE levels, Aβ pathology, and progression from aMCI to a clinical ADD diagnosis.

摘要

背景

血浆载脂蛋白 E（apoE）水平较低和存在 APOE ε4 等位基因与阿尔茨海默病（AD）风险增加有关。尽管 APOE ε4 携带者患 AD 的风险增加已得到充分证实，但对其蛋白水平的关注有限。

方法

我们在此报告了一个纵向（24 个月）随访队列的基线总血浆 apoE 和 apoE 同工型水平，该队列包括对照组（n=39）、24 个月随访期间稳定的遗忘型轻度认知障碍患者（MCI-MCI，n=30）、在随访期间被临床诊断为伴有痴呆的遗忘型 MCI（MCI-ADD，n=28）的患者和基线时患有 AD 伴痴呆（ADD，n=28）的患者。我们还评估了血浆 apoE 水平与脑脊液（CSF）AD 生物标志物和 α-突触核蛋白以及 CSF 和血浆神经丝轻链（NfL）、YKL-40 和激肽释放酶 6 之间的相关性。

结果

无论临床诊断如何，apoE ε2/ε3 与 apoE ε4/ε4 受试者的 apoE 水平最高，女性的差异最显著。与 MCI-ADD 和 ADD 患者相比，对照组的总血浆 apoE 水平分别高 32%和 21%。有趣的是，与 MCI-MCI 患者相比，MCI-ADD 患者的血浆 apoE 水平降低了 30%。这种减少似乎与大脑淀粉样蛋白-β（Aβ）病理学有关，无论使用淀粉样蛋白、tau 和神经退行性变（A/T/N）分类评估疾病状态如何。除了低血浆 apoE 与低 CSF Aβ 之间的关联外，较低的 apoE 水平还与更高水平的 CSF 总 tau（t-tau）和 Tau 磷酸化在苏氨酸 181 位（p-tau）和 NfL 以及更差的迷你精神状态检查表现有关。在 MCI-ADD 患者中，低水平的血浆 apoE 与更高水平的 CSF α-突触核蛋白和激肽释放酶 6 相关。未观察到血浆 apoE 与星形胶质细胞炎症标志物 YKL40 之间存在显著相关性。