在阿尔茨海默病高风险人群中，BDNF表达介导言语学习和记忆。

IF 4 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2025-01-16 eCollection Date: 2025-01-01 DOI:10.1002/dad2.70062

Kyle J Edmunds, Alyssa A Pandos, Isabella Hoang, Gabriella M Mamlouk, Alice Motovylyak, Sarah R Lose, Sanjay Asthana, Matthew Stremlau, Sterling C Johnson, Henriette van Praag, Ozioma C Okonkwo

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引用次数: 0

摘要

摘要：本研究探讨了血浆脑源性神经营养因子（BDNF）表达是否介导了言语学习和记忆（VLM）的性别差异。方法：在来自威斯康星州阿尔茨海默病预防登记处的n = 201名参与者（63.81±6.04岁，66.2%为女性，65.7%为阿尔茨海默病[AD]家族史，38%为载脂蛋白E [APOE] ε4+）的样本中，使用试验3至5和Rey听觉言语学习测试的延迟回忆来测量VLM。血浆BDNF采用人BDNF定量免疫分析法测定。中介分析采用自举法，分层中介模型检验APOE ε4携带的条件依赖性。结果：BDNF部分介导性- vlm关系(β = -0.07；95%置信区间[CI]: -0.18, -0.01)。女性APOE ε4携带者VLM评分较高(β = -0.53；p = 0.03)，而女性非携带者BDNF水平均较高(β = -0.68；讨论：本研究发现，循环BDNF介导女性更高的言语记忆分数，尤其是APOE ε4非携带者。重点：语言学习和记忆（VLM）的性别差异是由血浆脑源性神经营养因子（BDNF）水平介导的。与男性相比，女性表现出更高的VLM评分和血浆BDNF水平。载脂蛋白E ε4的携带减弱了BDNF对女性的保护作用。研究结果表明，在衰老过程中，针对语言记忆衰退的机制存在性别差异。

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BDNF expression mediates verbal learning and memory in women in a cohort enriched with risk for Alzheimer's disease.

Introduction: This study examined whether sex differences in verbal learning and memory (VLM) are mediated by plasma brain-derived neurotrophic factor (BDNF) expression.

Methods: In a sample of n = 201 participants (63.81 ± 6.04 years, 66.2% female, 65.7% family history of Alzheimer's disease [AD], 38% apolipoprotein E [APOE] ε4+) from the Wisconsin Registry for Alzheimer's Prevention, VLM was measured using trials 3 through 5 and delayed recall from the Rey Auditory Verbal Learning Test. Plasma BDNF was measured using a Human BDNF Quantikine Immunoassay. Mediation analysis used bootstrapping, and stratified mediation models tested the conditional dependence of APOE ε4 carriage.

Results: BDNF partially mediated the sex-VLM relationship (β = -0.07; 95% confidence interval [CI]: -0.18, -0.01). Female APOE ε4 carriers had higher VLM scores (β = -0.53; p = 0.03), while female non-carriers had both higher BDNF levels (β = -0.68; p < 0.01) and VLM scores (β = -1.06; p < 0.01); BDNF was again a significant mediator (β = -0.18; 95% CI: -0.37, -0.05).

Discussion: This study found that circulating BDNF mediates higher verbal memory scores in females-particularly in APOE ε4 non-carriers.

Highlights: Sex differences in verbal learning and memory (VLM) were mediated by plasma brain-derived neurotrophic factor (BDNF) levels.Women exhibited higher VLM scores and plasma BDNF levels compared to men.The protective effect of BDNF in women was attenuated by apolipoprotein E ε4 carriage.Findings suggest sex-specific mechanisms against verbal memory decline in aging.

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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.