Plasma biomarker trajectories: Impact of AD genetic risk and clinical progression.

IF 4.4 Q1 CLINICAL NEUROLOGY Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2025-03-27 eCollection Date: 2025-01-01 DOI:10.1002/dad2.70081

Corinne Pettigrew, Anja Soldan, Jiangxia Wang, Timothy Hohman, Logan Dumitrescu, Marilyn Albert, Kaj Blennow, Tobias Bittner, Abhay Moghekar

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Abstract

Introduction: We examined long-term plasma biomarker trajectories among participants who were cognitively unimpaired and primarily middle aged at baseline and whether trajectories differed by Alzheimer's disease (AD) genetic risk and among those who developed cognitive impairment.

Methods: Plasma amyloid beta (Aβ)₄₂/Aβ₄₀, phosphorylated tau (p-tau)₁₈₁, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), soluble triggering receptor expressed on myeloid cells, and chitinase 3-like protein 1 were measured longitudinally in 177 BIOCARD participants (M baseline age = 57.7 years; M follow-up = 15.8 years), including 57 who developed cognitive impairment. Measures of AD genetic risk included apolipoprotein E (APOE) ε4 and an AD polygenic risk score (AD-PRS).

Results: Compared to non-carriers, APOE ε4 carriers had lower Aβ₄₂/Aβ₄₀ and greater longitudinal increases in p-tau₁₈₁ and GFAP; in contrast, the AD-PRS (excluding the APOE region) was associated with greater declines in Aβ₄₂/Aβ₄₀ among APOE ε4 non-carriers. Rates of increase in p-tau₁₈₁, NfL, and GFAP were greater among those who later developed cognitive impairment.

Discussion: Monitoring changes in plasma p-tau₁₈₁, NfL, and GFAP may be particularly informative during preclinical AD.

Highlights: We examined plasma biomarker changes in cognitively normal individuals over 15.8 years.Apolipoprotein E (APOE) ε4 was related to lower amyloid beta (Aβ)₄₂/Aβ₄₀ and greater increases in phosphorylated tau (p-tau)₁₈₁ and glial fibrillary acidic protein (GFAP).In APOE ε4 non-carriers, higher Alzheimer's disease (AD) polygenic risk score was related to greater Aβ₄₂/Aβ₄₀ declines.P-tau₁₈₁, NfL, and GFAP increases were greater among those who progressed to mild cognitive impairment.Results highlight the predictive value of plasma biomarkers during preclinical AD.

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血浆生物标志物轨迹：AD遗传风险和临床进展的影响。

我们研究了基线时认知功能未受损且主要为中年人的受试者的长期血浆生物标志物轨迹，以及阿尔茨海默病（AD）遗传风险与认知功能受损受试者的轨迹是否存在差异。方法：纵向测量177名BIOCARD参与者(M基线年龄= 57.7岁；随访= 15.8年)，其中57例出现认知障碍。AD遗传风险指标包括载脂蛋白E (APOE) ε4和AD多基因风险评分（AD- prs）。结果：与非携带者相比，APOE ε4携带者Aβ42/Aβ40较低，p-tau181和GFAP纵向升高较大；相反，AD-PRS（不包括APOE区域）与APOE ε4非携带者中a - β42/ a - β40的更大下降相关。p-tau181、NfL和GFAP的增加率在后来出现认知障碍的人群中更大。讨论：监测血浆p-tau181、NfL和GFAP的变化可能在临床前AD期间提供特别的信息。重点：我们检查了15.8岁以上认知正常个体的血浆生物标志物变化。载脂蛋白E (APOE) ε4与淀粉样蛋白β (Aβ)42/Aβ40降低、磷酸化tau蛋白（p-tau）181和胶质纤维酸性蛋白（GFAP）升高有关。在APOE ε4非携带者中，阿尔茨海默病（AD）多基因风险评分越高，a - β42/ a - β40下降幅度越大。P-tau181、NfL和GFAP在进展为轻度认知障碍的患者中增加更大。结果强调了血浆生物标志物在临床前AD中的预测价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Medicine-Psychiatry and Mental Health

CiteScore

7.80

自引率

7.50%

发文量

101

审稿时长

8 weeks

期刊介绍： Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.