听觉脑干反应在5xFAD小鼠模型中诊断阿尔茨海默样病

IF 2.6 3区 医学 Q3 NEUROSCIENCES eNeuro Pub Date : 2025-04-23 Print Date: 2025-04-01 DOI:10.1523/ENEURO.0049-25.2025
Daxiang Na, Yidan Yang, Li Xie, Dorota Piekna-Przybylska, Dominic Bunn, Maleelo Shamambo, Patricia White
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引用次数: 0

摘要

早期和准确诊断阿尔茨海默病(AD)将是有效的个性化治疗计划的关键(Cummings, 2023)。轻度认知障碍(MCI)是阿尔茨海默病的前症(Tarawneh et al., 2022),在许多患有轻度认知障碍(MCI)的患者中,经常报道听觉处理存在显著困难,使其成为阿尔茨海默病诊断生物标志物的杰出候选者。然而,使用该参数的诊断效率尚未得到探讨。当患有淀粉样变的雄性小鼠开始表现出记忆力下降时,听觉脑干反应(ABR)对点击的变化使使用机器学习算法可靠地诊断疾病成为可能。对机器学习诊断的解释显示,听觉通路的上层,包括下丘,是缺陷的可能来源。组织学分析表明,在这些部位,神经炎症和斑块沉积与与记忆丧失一致的行为改变在时间上相关。虽然这些发现受到来自淀粉样变小鼠的警告的影响,但我们建议将ABR测量作为一种额外的快速、低成本、非侵入性的生物标志物进行评估,以协助早期AD的诊断测试。新的AD疾病修饰疗法只对一部分患者有效,并且需要精确的疾病分期。阿尔茨海默病与中枢性听觉功能障碍和听力损失高度相关,但这些都不是诊断性的。我们发现被动听觉脑干反应测试的特征可靠地诊断AD小鼠模型的记忆衰退,与淀粉样蛋白沉积和上听核神经炎症的开始相关。我们进一步强调了一个区域,即下丘,在多感觉整合中所起的作用,并推测当斑块负担的皮层无法补偿前意识感觉加工的退化时,痴呆症就会变得明显。
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The Auditory Brainstem Response Diagnoses Alzheimer-Like Disease in the 5xFAD Mouse Model.

Early and accurate diagnosis of Alzheimer's disease (AD) will be key for effective personalized treatment plans ( Cummings, 2023). Significant difficulties in auditory processing have been frequently reported in many patients with mild cognitive impairment, the prodromal form of AD ( Tarawneh et al., 2022), making it an outstanding candidate as AD diagnostic biomarker. However, the efficiency of diagnosis with this parameter has not been explored. Here we show that when male mice with amyloidosis begin to show memory decline, changes in the auditory brainstem response (ABR) to clicks enable the reliable diagnosis of disease using a machine learning algorithm. Interpretation of the machine learning diagnosis revealed that the upper levels of the auditory pathway, including the inferior colliculus, were the probable sources of the defects. Histological analyses show that in these locations, neuroinflammation and plaque deposition temporally correlate with behavioral changes consistent with memory loss. While these findings are tempered by the caveat that they derive from amyloidosis mice, we propose that ABR measurements be evaluated as an additional rapid, low-cost, noninvasive biomarker to assist the diagnostic testing of early-stage AD.

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来源期刊
eNeuro
eNeuro Neuroscience-General Neuroscience
CiteScore
5.00
自引率
2.90%
发文量
486
审稿时长
16 weeks
期刊介绍: An open-access journal from the Society for Neuroscience, eNeuro publishes high-quality, broad-based, peer-reviewed research focused solely on the field of neuroscience. eNeuro embodies an emerging scientific vision that offers a new experience for authors and readers, all in support of the Society’s mission to advance understanding of the brain and nervous system.
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