认知未受损个体血浆中阿尔茨海默病生物标志物与认知衰退的关联。

Association of plasma Alzheimer's disease biomarkers with cognitive decline in cognitively unimpaired individuals.

作者信息

Cogswell Petrice M, Wiste Heather J, Therneau Terry M, Griswold Michael E, Mattsson-Carlgren Niklas, Palmqvist Sebastian, Binette Alexa Pichet, Stomrud Erik, Bateman Randall J, Barthelemy Nicolas, Braunstein Joel B, West Tim, Verghese Philip B, Machulda Mary M, Graff-Radford Jonathan, Algeciras-Schimnich Alicia, Lowe Val J, Schwarz Christopher G, Senjem Matthew L, Gunter Jeffrey L, Knopman David S, Vemuri Prashanthi, Petersen Ronald C, Hansson Oskar, Jack Clifford R

机构信息

Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.

Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.

出版信息

Alzheimers Dement. 2025 Sep;21(9):e70625. doi: 10.1002/alz.70625.

DOI:10.1002/alz.70625

PMID:40883967

Abstract

INTRODUCTION

Plasma biomarkers' utility for predicting incident mild cognitive impairment (MCI) remains unclear. We evaluated associations of plasma Alzheimer's disease (AD) biomarkers and amyloid positron emission tomography (PET) with transitions from cognitively unimpaired (CU) to MCI in the Mayo Clinic Study of Aging (MCSA) and BioFINDER-2 studies.

METHODS

Associations of continuous baseline plasma biomarker levels and amyloid PET Centiloid with progression to MCI, adjusting for age, sex, and education, were evaluated with Cox proportional hazards models.

RESULTS

The study included 381 MCSA and 584 BioFINDER-2 participants. Amyloid PET and percent phosphorylated to non-phosphorylated tau217 (%p-tau217) were strong predictors of progression to MCI in both cohorts: hazard ratios of 1.49 and 1.23 in the MCSA and 1.72 and 1.65 in BioFINDER, respectively. Amyloid beta 42/40 was a significant predictor in BioFINDER-2 only (hazard ratio 2.20).

DISCUSSION

Plasma %p-tau217 was associated with progression from CU to MCI in both cohorts, although differences in biomarker associations may be related to differences in the two cohorts.

HIGHLIGHTS

Mass-spectrometry-based plasma phosphorylated tau217 was associated with cognitively unimpaired to mild cognitive impairment (MCI) progression. Plasma amyloid beta 42/40 was a significant predictor in BioFINDER but not the Mayo Clinic Study of Aging (MCSA). Amyloid positron emission tomography (PET) was the strongest predictor of progression to MCI in the MCSA. Plasma had added value to amyloid PET in BioFINDER but not the MCSA. Biomarker performance may vary with cohort and biomarker measurement differences.

摘要

引言

血浆生物标志物在预测轻度认知障碍（MCI）发病方面的效用仍不明确。在梅奥诊所衰老研究（MCSA）和BioFINDER - 2研究中，我们评估了血浆阿尔茨海默病（AD）生物标志物及淀粉样蛋白正电子发射断层扫描（PET）与从认知未受损（CU）转变为MCI之间的关联。

方法

采用Cox比例风险模型评估连续的基线血浆生物标志物水平及淀粉样蛋白PET Centiloid与进展为MCI之间的关联，并对年龄、性别和教育程度进行校正。

结果

该研究纳入了381名MCSA参与者和584名BioFINDER - 2参与者。淀粉样蛋白PET及磷酸化tau217与非磷酸化tau217的百分比（%p - tau217）在两个队列中均是进展为MCI的强预测指标：在MCSA队列中风险比分别为1.49和1.23，在BioFINDER队列中分别为1.72和1.65。淀粉样蛋白β42/40仅在BioFINDER - 2中是显著的预测指标（风险比2.20）。

讨论

在两个队列中，血浆%p - tau217均与从CU进展为MCI相关，尽管生物标志物关联的差异可能与两个队列的差异有关。

要点

基于质谱的血浆磷酸化tau217与从认知未受损进展为轻度认知障碍（MCI）相关。血浆淀粉样蛋白β42/40在BioFINDER中是显著的预测指标，但在梅奥诊所衰老研究（MCSA）中不是。淀粉样蛋白正电子发射断层扫描（PET）在MCSA中是进展为MCI的最强预测指标。在BioFINDER中血浆对淀粉样蛋白PET有附加价值，但在MCSA中没有。生物标志物的表现可能因队列和生物标志物测量差异而有所不同。