双相障碍相关阿尔茨海默病生物标志物的纵向一年病例对照研究。

Alzheimer's disease related biomarkers in bipolar disorder - A longitudinal one-year case-control study.

机构信息

Psychiatric Center Copenhagen, Department Rigshospitalet, Copenhagen Affective Disorder Research Center (CADIC), Blegdamsvej 9, 2100 Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Danish Dementia Research Center, Rigshospitalet, Copenhagen, Denmark.

出版信息

J Affect Disord. 2022 Jan 15;297:623-633. doi: 10.1016/j.jad.2021.10.074. Epub 2021 Oct 31.

DOI:10.1016/j.jad.2021.10.074

PMID:34728295

Abstract

INTRODUCTION

Bipolar disorder (BD) is a heterogeneous mental disorder characterized by recurrent relapses of affective episodes: Subgroups of patients with BD have cognitive deficits, and an increased risk of dementia.

METHODS

This prospective, longitudinal, one-year follow-up, case-control study investigated biomarkers for AD and neurodegenerative diseases, namely: cerebrospinal fluid (CSF) amyloid beta (Aβ) isoforms and ratios (Aβ42, Aβ40, Aβ38), CSF soluble amyloid precursor protein (sAPP) α and β, CSF total (t-tau) and phosphorylated tau (p-tau), CSF neurofilament-light (NF-L), CSF neurogranin (NG), plasma-isoforms Aβ42 and Aβ40, plasma-tau, plasma-NF-L, and serum S100B, in patients with BD (N = 62, aged 18-60) and gender-and-age-matched healthy control individuals (N = 40). CSF and plasma/serum samples were collected at baseline, during and after an affective episode, if it occurred, and after a year. Data were analyzed in mixed models.

RESULTS

Levels of CSF Aβ42 decreased in patients with BD who had an episode during follow-up (BD-E) (N = 22) compared to patients without an episode (BD-NE) (N = 25) during follow-up (P = 0.002). Stable levels were seen for all other markers in BD-E compared to BD-NE during the one-year follow-up. We found no statistically significant differences between patients with BD and HC at T0 and T3 for Aβ42, Aβ40, Aβ38, Aβ42/38, Aβ42/40, sAPPα, sAPPβ, t-tau, p-tau, p-tau /t-tau, NF-L, NG in CSF and further Aβ40, Aβ42, Aβ42/40, t-tau, NF-L in plasma, S100B in serum, and APOE-status. Furthermore, all 18 biomarkers were stable in HC during the one-year follow-up from T0 to T3.

CONCLUSION

A panel of biomarkers of Alzheimer's and neurodegeneration show no differences between patients with BD and HC. There were abnormalities of amyloid production/clearance during an acute BD episode. The abnormalities mimic the pattern seen in AD namely decreasing CSF Aβ42 and may suggest an association with brain amyloidosis.

摘要

简介

双相障碍（BD）是一种异质性精神障碍，其特征为情感发作的反复发作：BD 患者存在认知缺陷和痴呆风险增加的亚组。

方法

这项前瞻性、纵向、为期一年的随访、病例对照研究调查了 AD 和神经退行性疾病的生物标志物，即：脑脊液（CSF）淀粉样β（Aβ）异构体和比值（Aβ42、Aβ40、Aβ38）、CSF 可溶性淀粉样前体蛋白（sAPP）α和β、CSF 总（t-tau）和磷酸化 tau（p-tau）、CSF 神经丝轻链（NF-L）、CSF 神经颗粒蛋白（NG）、血浆 Aβ42 和 Aβ40 异构体、血浆 tau、血浆 NF-L 和血清 S100B，在患有 BD（N=62，年龄 18-60 岁）和性别及年龄匹配的健康对照个体（N=40）中。在基线时、发作期间和发作后（如果发作）以及一年后采集 CSF 和血浆/血清样本。数据采用混合模型进行分析。

结果

在随访期间出现发作的 BD 患者（BD-E）（N=22）与未出现发作的 BD 患者（BD-NE）（N=25）相比，CSF Aβ42 水平在随访期间下降（P=0.002）。在为期一年的随访期间，BD-E 患者与 BD-NE 患者相比，所有其他标志物的水平均保持稳定。在 T0 和 T3 时，我们未发现 BD 患者和 HC 患者之间的 Aβ42、Aβ40、Aβ38、Aβ42/38、Aβ42/40、sAPPα、sAPPβ、t-tau、p-tau、p-tau/t-tau、NF-L、NG 在 CSF 中存在统计学差异，并且在 Aβ40、Aβ42、Aβ42/40、t-tau、NF-L 在血浆中，S100B 在血清中以及 APOE 状态无统计学差异。此外，在从 T0 到 T3 的一年随访期间，所有 18 种生物标志物在 HC 中均保持稳定。