Neurobiology of Aging最新文献_第3页

Editorial Advisory Board 编辑顾问委员会

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-12-06 DOI: 10.1016/S0197-4580(25)00205-2

引用次数: 0

White matter hyperintensity regression: Fact or artifact? 白质高强度回归：事实还是假象？

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-12-03 DOI: 10.1016/j.neurobiolaging.2025.12.002

Ahmed A. Bahrani , Peter T. Nelson , Erin L. Abner , David K. Powell , Christopher M. Norris , Elif Pinar Coskun , Ann M. Stowe , Larry B. Goldstein , Linda J. Van Eldik , Brian T. Gold , Donna M. Wilcock , Charles S. DeCarli , Steven M. Greenberg , Gregory A. Jicha

White matter hyperintensities (WMH) are an MRI-based biomarker associated with aging, Alzheimer’s disease, and vascular dementia. Although the volume of WMH typically increases over time (growth) for individuals, WMH volume in some cases can also decrease (regress). This suggests the presence of active brain injury recovery mechanisms. Whether WMH regression reflects a true biological phenomenon or results from imaging artifacts or measurement errors, however, remains controversial. Here, we review published reports, following PRISMA search guidelines, describing or referring to WMH regression, the methods used to detect and quantitate regression, and proposed underlying mechanisms. Of 174 reviewed articles, 31 (26 original research studies and five case reports) were identified as directly related to WMH regression. Technical factors such as differences in longitudinal scan parameters, motion artifacts, and the interval between baseline and follow-up scans can affect WMH volume measurements. These factors may lead to inaccurate conclusions if appropriate controls are not employed. Although the use of standardized and systematic measurement protocols is essential, there is strong evidence indicating that WMH regression is a robust and biologically important phenomenon that may be influenced by clinical interventions. Further studies are needed to investigate WMH regression in relation to cerebrovascular risk mitigation and other therapeutic strategies.

白质高强度（WMH）是一种基于mri的生物标志物，与衰老、阿尔茨海默病和血管性痴呆相关。虽然WMH的体积通常会随着时间的推移而增加（生长），但在某些情况下WMH体积也会减少（退化）。这表明存在活跃的脑损伤恢复机制。然而，WMH回归是否反映了真实的生物现象或成像伪影或测量误差的结果仍然存在争议。在这里，我们回顾了已发表的报告，遵循PRISMA搜索指南，描述或参考WMH回归，用于检测和量化回归的方法，并提出了潜在的机制。在174篇综述文章中，31篇（26篇原创研究和5篇病例报告）被确定为与WMH回归直接相关。技术因素，如纵向扫描参数的差异、运动伪影以及基线和后续扫描之间的间隔，都会影响WMH体积测量。如果不采取适当的控制措施，这些因素可能导致不准确的结论。虽然使用标准化和系统的测量方案是必不可少的，但有强有力的证据表明，WMH回归是一种强大的、生物学上重要的现象，可能受到临床干预措施的影响。需要进一步研究WMH回归与脑血管风险缓解和其他治疗策略的关系。

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引用次数: 0

PS19 mouse tauopathy is associated with sex-dependent sleep loss and hyperarousal, and predicts cognitive performance PS19小鼠tau病与性别依赖性睡眠缺失和过度觉醒有关，并预测认知表现。

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-12-03 DOI: 10.1016/j.neurobiolaging.2025.12.001

Jarrah O.Z.J. Kron , Jeremy A. Metha , Heather J. Daykin , Leigh C. Walker , Yasmin Potts , Giancarlo Allocca , Ryan J. Keenan , Daniel Hoyer , Laura H. Jacobson

Alzheimer’s disease (AD) is a major public health concern in societies with increasingly ageing populations. Accumulating evidence implies a specific link between the development of tauopathy, cognitive impairment, and sleep loss in AD patients. P301S mutant tau-transgenic (PS19) mice, modelling frontotemporal dementia (FTD) and AD tauopathy, demonstrate sleep loss and cognitive impairment. We aimed to assess the progression of sleep loss and cognitive decline longitudinally in both sexes of PS19 mice. WT and PS19 mice underwent polysomnography (PSG), electroencephalography (EEG) power spectral analysis, locomotor activity assessments at 7, 8 and 9-months of age, and Barnes maze testing at 7 and 9-months. PS19s demonstrated profound sleep loss, and locomotor hyperarousal; paralleling observations in AD patients and other studies of mouse tauopathy. This phenotype was more pronounced in PS19 males than females. WT and PS19 mice showed similar learning in repeated Barnes maze testing at 9-months. At 9-months of age, cognitive performance was best predicted by 7-month locomotor hyperarousal, 9-month EEG power outcomes in wakefulness frequency bands associated with cognition, and balanced physiological NREM and REM sleep. Our longitudinal design revealed that researchers should consider early sleep disruption, hyperarousal, and wakeful EEG power in combination as predictors of cognitive symptoms related to tauopathy. Further investigation into mechanisms to promote balanced sleep, which maintain both NREM and REM sleep with ageing, is indicated as a mechanism to potentially preserve cognition in neurodegenerative disorders.

在人口日益老龄化的社会中，阿尔茨海默病（AD）是一个主要的公共卫生问题。越来越多的证据表明，AD患者的牛头病、认知障碍和睡眠缺失之间存在特定的联系。P301S突变型tau转基因（PS19）小鼠，模拟额颞叶痴呆（FTD）和AD tau病变，表现出睡眠不足和认知障碍。我们旨在纵向评估PS19小鼠两性睡眠缺失和认知能力下降的进展。WT和PS19小鼠分别在7、8和9月龄时进行多导睡眠图（PSG）、脑电图（EEG）功率谱分析、运动活动评估，并在7和9月龄时进行巴恩斯迷宫测试。ps19表现出严重的睡眠缺失和运动性亢奋；在AD患者和其他小鼠病变研究中的平行观察。这种表型在PS19雄性中比雌性更明显。WT和PS19小鼠在9月龄时的重复巴恩斯迷宫测试中表现出相似的学习能力。在9个月大时，7个月的运动过度觉醒、9个月与认知相关的清醒频带的脑电图功率结果以及平衡的生理非快速眼动和快速眼动睡眠可以最好地预测婴儿的认知表现。我们的纵向设计显示，研究人员应该考虑早期睡眠中断、过度觉醒和清醒时脑电图功率的组合，作为与牛头病相关的认知症状的预测因素。对促进平衡睡眠机制的进一步研究表明，随着年龄的增长，平衡睡眠可以维持非快速眼动和快速眼动睡眠，这可能是神经退行性疾病患者保持认知的潜在机制。

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引用次数: 0

Electroencephalography, pupillometry, and behavioral evidence for locus coeruleus-noradrenaline system related tonic hyperactivity in older adults 老年人蓝斑-去甲肾上腺素系统相关的紧张性多动症的脑电图、瞳孔测量和行为证据

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-11-29 DOI: 10.1016/j.neurobiolaging.2025.11.008

Andy Jeesu Kim , Santiago Morales , Joshua Senior , Mara Mather

Neuroimaging studies have shown that age-related dysregulation of the locus coeruleus-noradrenaline (LC-NA) system is associated with cognitive decline. However, due to limitations in directly measuring LC function in vivo, it remains unclear whether age-related alterations in humans reflect tonic LC-NA system hyper- or hypoactivity, constraining our understanding of underlying mechanisms and hampering the development of targeted preventative interventions. In this study, we acquired electrophysiological, pupillometric, and behavioral measures in a passive and active auditory oddball paradigm to test the hypothesis that cognitively healthy older adults experience tonic LC hyperactivity. We leveraged the LC-NA system’s role in arousal regulation and manipulated state arousal and noradrenergic activity using the unpredictable threat of electric shock. Based on older adults' hypothesized tonic LC hyperactivity, we predicted that increased arousal would evoke weaker phasic (stimulus-evoked) noradrenergic responses in older adults compared with young adults. Consistent with this hypothesis, arousal differentially modulated behavioral responses and resting-state alpha power across age groups, and older adults showed smaller pupil dilation responses than young adults. Furthermore, linear mixed models revealed that arousal differentially modulated attentional control to salient but task-irrelevant distractors across age groups, with older adults exhibiting less behavioral slowing and longer P300 latency delays under threat of shock than did young adults. Together these findings provide convergent multi-modal evidence that aging is associated with tonic LC-NA system hyperactivity in humans, with consequences for mechanisms supporting attentional control. This research highlights the utility of non-invasive physiological markers to determine when across the adult lifespan the LC-NA system becomes hyperactive and to identify adults who may be at elevated risk for neurodegenerative progression due to emerging changes in LC-NA system function.

神经影像学研究表明，蓝斑-去甲肾上腺素（LC-NA）系统的年龄相关失调与认知能力下降有关。然而，由于直接测量体内LC功能的局限性，目前尚不清楚人类年龄相关的改变是否反映了强直性LC- na系统的高活性或低活性，这限制了我们对潜在机制的理解，并阻碍了有针对性的预防干预措施的发展。在这项研究中，我们在被动和主动听觉怪异范式中获得了电生理、瞳孔测量和行为测量，以检验认知健康的老年人经历强直性左脑多动的假设。我们利用LC-NA系统在唤醒调节中的作用，并利用不可预测的电击威胁来操纵状态唤醒和去肾上腺素能活动。基于老年人假设的强直性LC亢进，我们预测与年轻人相比，老年人觉醒的增加会引起较弱的阶段性（刺激诱发的）去肾上腺素能反应。与这一假设相一致，唤醒对不同年龄组的行为反应和静息状态α功率的调节存在差异，老年人的瞳孔扩张反应比年轻人小。此外，线性混合模型揭示了不同年龄组的唤醒对显著但与任务无关的干扰物的注意控制的差异调节，老年人在电击威胁下表现出更少的行为减慢和更长的P300潜伏期延迟。总之，这些发现提供了趋同的多模态证据，表明衰老与人类的强直性LC-NA系统过度活跃有关，并对支持注意力控制的机制产生影响。本研究强调了非侵入性生理标记的实用性，以确定在整个成人生命周期中LC-NA系统何时变得过度活跃，并识别由于LC-NA系统功能的新变化而可能处于神经退行性进展风险升高的成年人。

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引用次数: 0

Time-restricted feeding rescues sociability deficits and reduces neuroinflammation in aged mice 限时喂养可以缓解老年小鼠的社交缺陷，并减少神经炎症

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-11-27 DOI: 10.1016/j.neurobiolaging.2025.11.007

Louise M. Ince , Brandy N. Routh , Jeffrey S. Darling , Krishi Manem , Akshay Prabhakar , Sophia Martinez , Emily Chan , Ruizhuo Chen , Andrew D. Gaudet , Laura K. Fonken

The aging brain exhibits an increased inflammatory potential which in turn elicits behavioral changes e.g., social withdrawal. Social isolation is a risk factor for additional health complications, and interventions which can mitigate these negative facets of aging can improve longevity and quality of life in old age. The circadian system critically regulates neuroimmune function and behavior, but circadian rhythms also degrade with age, resulting in lower amplitude oscillations in activity and hormone secretion. Time-restricted feeding (TRF), in which food availability is limited to a specific time-of-day, is a simple dietary intervention which provides timing cues to the circadian system - protecting against metabolic disease and reducing systemic inflammation. We thus tested the hypothesis that TRF could serve as an intervention to bolster circadian rhythms in aged mice and have beneficial effects upon age-associated neuroinflammation and behavior. Here, we demonstrate that 6 weeks of TRF in aged (18 months old) mice ameliorates age-associated social withdrawal and drives distinct molecular and cellular changes within the brain. TRF attenuates age-associated increases in inflammatory gene expression in the hippocampus and prefrontal cortex, and re-establishes circadian phase-appropriate expression of autophagy-related genes in the hippocampus. In addition, TRF promotes a diurnal rhythm in microglial branching complexity in the hippocampus, recapitulating the pattern observed in young adults (3 months old). TRF also reduced blood glucose levels in aged males, but not in aged females, suggesting sex-specific effects on metabolic parameters with age. These results highlight the efficacy of TRF as a therapeutic approach to alleviate age-associated neuroinflammation and social withdrawal.

衰老的大脑表现出增加的炎症潜力，从而引发行为变化，如社交退缩。社会孤立是造成更多健康并发症的一个风险因素，能够减轻老龄化这些负面影响的干预措施可以延长老年人的寿命和提高他们的生活质量。昼夜节律系统对神经免疫功能和行为起着关键的调节作用，但昼夜节律也会随着年龄的增长而退化，导致活动和激素分泌的振幅波动降低。限时喂养（TRF）是一种简单的饮食干预，它为昼夜节律系统提供时间线索，防止代谢疾病和减少全身炎症。限时喂养是指在一天中的特定时间内提供食物。因此，我们测试了TRF可以作为一种干预措施来增强老年小鼠的昼夜节律，并对与年龄相关的神经炎症和行为产生有益影响的假设。在这里，我们证明了6周的TRF在老年（18个月大）小鼠中改善了与年龄相关的社交退缩，并驱动了大脑中明显的分子和细胞变化。TRF减弱了海马和前额叶皮层中炎症基因表达的年龄相关性增加，并在海马中重新建立了自噬相关基因的昼夜节律相适应表达。此外，TRF促进了海马体中小胶质分支复杂性的昼夜节律，再现了在年轻人（3个月大）中观察到的模式。TRF还能降低老年男性的血糖水平，但对老年女性没有作用，这表明性别对代谢参数的影响随年龄而异。这些结果强调了TRF作为一种治疗方法的有效性，以减轻与年龄相关的神经炎症和社交退缩。

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引用次数: 0

Lysophosphatidic acid derivative is a novel candidate of therapeutic agents for a mouse model of frontotemporal dementia with progranulin deficiency 溶血磷脂酸衍生物是一种新的候选治疗小鼠额颞叶痴呆伴蛋白前缺乏模型的药物

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-11-24 DOI: 10.1016/j.neurobiolaging.2025.11.006

Nami Yamamoto , Rino Takei , Mari Gotoh , Yasunori Miyamoto , Kei Hashimoto

Frontotemporal dementia (FTD) is driven by progranulin haploinsufficiency, in which age-dependent microglial activation promotes neurodegeneration through TDP-43 proteinopathy. Cyclic phosphatidic acid (cPA) is a natural phospholipid mediator characterized by a unique cyclic phosphate ring at the sn-2 and sn-3 positions of its glycerol backbone. A pharmacologically active derivative of cPA has been shown to suppress microglial activation. Based on this, we aimed to investigate the potential of cPA derivatives to prevent the onset of FTD. Specifically, we administered metabolically stabilized cPA derivatives, 2-carba-cPA (2ccPA) and its degradation product, 2-carba-LPA (2cLPA), to presymptomatic progranulin-deficient (Grn^-/-) mice. The mice received intraperitoneal injections of 0.9 mg/kg/day of either compound for 6 months. Treatment with 2ccPA, but not 2cLPA, significantly attenuated thalamic neuronal loss, cytoplasmic TDP-43 aggregation, and microglial activation, including reduced transition to an ameboid morphology. These findings led us to hypothesize that 2ccPA mitigates disease onset by suppressing microglial activation. To test this, we examined the effects of 2ccPA on primary Grn^-/- microglia and found that treatment reduced markers of accelerated senescence, phagocytic activity, lipid accumulation, and CCL8 secretion. Collectively, our findings identify 2ccPA as a promising candidate for the prevention of FTD. This study also represents a conceptual advance by demonstrating that targeting microglial activation is an effective strategy to delay or attenuate neurodegeneration in FTD.

额颞叶痴呆（FTD）是由粒前蛋白单倍不全驱动的，其中年龄依赖性小胶质细胞激活通过TDP-43蛋白病变促进神经退行性变。环磷脂酸（cPA）是一种天然磷脂介质，其甘油主链sn-2和sn-3位置上有一个独特的环状磷酸环。药理活性衍生物的cPA已被证明抑制小胶质细胞的激活。基于此，我们旨在研究cPA衍生物预防FTD发病的潜力。具体来说，我们将代谢稳定的cPA衍生物2-碳巴-cPA （2ccPA）及其降解产物2-碳巴- lpa （2cLPA）给予症状前颗粒蛋白前缺陷（Grn-/-）小鼠。小鼠腹腔注射任意一种化合物0.9 mg/kg/天，持续6个月。2ccPA治疗，而不是2cLPA治疗，显著减轻丘脑神经元丢失、胞质TDP-43聚集和小胶质细胞活化，包括减少向变形虫形态的转变。这些发现使我们假设2ccPA通过抑制小胶质细胞的激活来减轻疾病的发作。为了验证这一点，我们检查了2ccPA对初级Grn-/-小胶质细胞的影响，发现治疗降低了加速衰老、吞噬活性、脂质积累和CCL8分泌的标记物。总的来说，我们的研究结果确定2ccPA是预防FTD的有希望的候选药物。这项研究也代表了一个概念上的进步，证明靶向小胶质细胞激活是延迟或减轻FTD神经退行性变的有效策略。

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引用次数: 0

Editorial Advisory Board 编辑顾问委员会

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-11-18 DOI: 10.1016/S0197-4580(25)00194-0

引用次数: 0

Childhood maltreatment alters associations between age and neurocognitive health metrics in community-dwelling adults 儿童虐待改变了社区居住成年人年龄与神经认知健康指标之间的关系。

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-11-13 DOI: 10.1016/j.neurobiolaging.2025.11.004

Anna D. Stumps , Nadia Bounoua , Naomi Sadeh

To further understand whether childhood maltreatment (CM) is associated with indicators of accelerated cognitive aging, this study investigated whether CM moderated the relationship of age with gray matter volume (GMV) and executive functions among community adults aged 21–55. Participants (N = 225) underwent MRI scanning, and a composite measure of executive functions was computed across measures of inhibitory control, switching, and working memory. To interpret interactions, we created high (66th percentile) and low (33rd percentile) CM exposure groups and examined age-related variance in GMV and executive functions in each group. Vertex-wise cortical analysis revealed CM by age interactions in two right prefrontal cortex clusters [rostral middle frontal gyrus and superior frontal gyrus], where age negatively correlated with GMV at low CM (ps < 0.001), but this effect weakened at high CM (ps = 0.095–0.436). Further, a multivariate analysis of five subcortical regions revealed a CM-by-age interaction (p = 0.007), whereby age correlated negatively with GMV at high, but not low, CM. Finally, CM moderated the association between age and an executive functioning composite (p = 0.027), with age correlating more negatively with executive functions in individuals reporting high than low CM. Together, these cross-sectional findings suggest CM may influence age-related neurocognitive changes.

为了进一步了解儿童虐待是否与认知加速老化相关，本研究在21-55岁的社区成年人中调查了儿童虐待是否调节年龄与灰质体积（GMV）和执行功能的关系。参与者（N = 225）接受了MRI扫描，并通过抑制控制、转换和工作记忆的测量计算了执行功能的综合测量。为了解释相互作用，我们创建了高（第66百分位）和低（第33百分位）CM暴露组，并检查了每组中GMV和执行功能的年龄相关差异。脑皮层顶点分析显示，CM通过年龄在两个右侧前额叶皮层簇[额侧中回和额上回]中的相互作用，其中年龄与GMV在低CM时呈负相关（ps < 0.001），但在高CM时这种作用减弱（ps = 0.095-0.436）。此外，对5个皮质下区域的多变量分析显示CM与年龄的相互作用（p = 0.007），即年龄与GMV在CM高而不低时呈负相关。最后，CM调节了年龄和执行功能之间的关联（p = 0.027），在报告CM高的个体中，年龄与执行功能的负相关程度高于报告CM低的个体。总之，这些横断面研究结果表明CM可能影响与年龄相关的神经认知变化。

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引用次数: 0

Depressive symptoms and plasma AT(N) biomarkers among cognitively healthy and mild cognitively impaired in a diverse cohort 认知健康和轻度认知受损人群的抑郁症状和血浆AT(N)生物标志物

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-11-13 DOI: 10.1016/j.neurobiolaging.2025.11.005

Christina S. Dintica , Leigh Johnson , Melissa Petersen , Sid O’Bryant , Kristine Yaffe

Depression is a known risk factor for dementia and MCI, but its associations with AT(N) biomarkers remain inconsistent and may differ by cognitive status. We cross-sectionally studied 2929 dementia-free participants from the Health & Aging Brain Study—Health Disparities (HABS-HD). Mild cognitive impairment (MCI) was identified as having cognitive complaints, Clinical Dementia Rating scores between 0.5 and 2.0, and at least one cognitive test ≤ 1.5 SD below norms. We defined AT (N) with plasma biomarkers amyloid-β 42/40 (Aβ42/40), phosphorylated tau (p-tau181), neurofilament light (NfL), assessed using SIMOA technology and magnetic resonance imaging (MRI) based Alzheimer disease (AD) signature cortical thickness. Depressive symptoms were measured with the Geriatric Depression Scale (GDS), categorized as high (≥10) or low (<10). We used linear regression to determine association between depressive symptoms and biomarkers, adjusting for age, sex, education, kidney function, and body mass index. High depressive symptoms (19 %) were linked to higher NfL (standardized mean differences [SMD] = 0.10, 95 % confidence interval [CI: 0.02–0.18] and p-tau181 (SMD = 0.15, 95 % CI: 0.07–0.22) levels compared to low symptoms but not with Aβ42/40 or AD cortical thickness. Participants with both MCI and high depressive symptoms had higher NfL (SMD = 0.19, 95 % CI: 0.05–0.33) and p-tau181 (SMD = 0.30, 95 % CI: 0.16–0.45), and lower AD signature cortical thickness (SMD = –0.30, 95 % CI: –0.48 to –0.11). No group differences were found for Aβ42/40. Depressive symptoms, particularly among those with MCI, were linked to greater tau and neurodegeneration; longitudinal studies are needed to clarify this clinical significance.

抑郁症是痴呆和轻度认知障碍的已知危险因素，但其与AT(N)生物标志物的关联仍然不一致，可能因认知状态而异。我们横断面研究了2929名来自健康与衰老大脑研究-健康差异（HABS-HD）的无痴呆参与者。轻度认知障碍（MCI）被确定为有认知主诉，临床痴呆评分在0.5到2.0之间，至少有一项认知测试≤ 1.5 SD低于规范。我们用血浆生物标志物淀粉样蛋白-β 42/40 （Aβ42/40）、磷酸化tau蛋白（p-tau181）、神经丝光（NfL）来定义AT (N)，并使用SIMOA技术和基于阿尔茨海默病（AD）特征的磁共振成像（MRI）皮质厚度进行评估。用老年抑郁量表（GDS）测量抑郁症状，分为高（≥10）和低（<10）。我们使用线性回归来确定抑郁症状与生物标志物之间的关系，调整年龄、性别、教育程度、肾功能和体重指数。与低症状相比，高抑郁症状（19 %）与较高的NfL(标准化平均差异[SMD] = 0.10, 95 %可信区间[CI: 0.02-0.18]和p-tau181 （SMD = 0.15, 95 % CI: 0.07-0.22）水平相关，但与Aβ42/40或AD皮质厚度无关。MCI和高抑郁症状的参与者具有较高的NfL （SMD = 0.19, 95 % CI: 0.05-0.33）和p-tau181 （SMD = 0.30, 95 % CI: 0.16-0.45）和较低的AD特征皮质厚度（SMD = -0.30, 95 % CI: -0.48至-0.11）。Aβ42/40无组间差异。抑郁症状，尤其是轻度认知障碍患者，与较大的tau蛋白和神经变性有关；需要纵向研究来阐明这一临床意义。

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引用次数: 0

1H-MR spectroscopy biomarkers are associated with plasma-derived biomarkers of amyloid-β and tau in the early phase of AD continuum 在AD连续体的早期阶段，1H-MR光谱生物标志物与血浆来源的淀粉样蛋白-β和tau生物标志物相关

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-11-10 DOI: 10.1016/j.neurobiolaging.2025.11.003

Firat Kara , James M. Joers , Scott A. Przybelski , Alicia Algeciras-Schimnich , Jeffrey L. Gunter , Clifford R. Jack Jr , Ronald C. Petersen , Gülin Öz , Kejal Kantarci

The objective of the study was to evaluate the relationship of plasma biomarkers of Alzheimer’s disease (AD) with in vivo proton magnetic resonance spectroscopy (¹H-MRS) markers, and their association with cognitive function across the early stages of the AD continuum. Determining these associations may clarify the AD-related biological pathways and support the development of integrated AD blood and ¹H-MRS biomarkers for early detection of these pathways. Fifty-five older adults (40 cognitively unimpaired; 15 mild cognitive impairment) from the Mayo Clinic Study of Aging underwent single-voxel ¹H-MRS (sLASER) at 3T in the posterior cingulate gyrus (PCG) and left hippocampus (LH), along with plasma assays for Aβ42/40, phosphorylated tau (p-tau181), and the p-tau181/Aβ42 ratio. Associations between plasma biomarkers and ¹H-MRS metabolites (myo-inositol [mIns]/total creatine [tCr], total N-acetylaspartate [tNAA]/tCr, and tNAA/mIns) were examined using partial Spearman correlations (rho, ρ) adjusted for age and sex. Next, associations of the Mini-Mental State Examination with p-tau181/Aβ42 and tNAA/mIns were examined adjusting for the same covariates plus education. In both PCG and LH regions, lower tNAA/mIns was associated with higher p-tau181/Aβ42 (PCG:ρ=−0.59; LH:ρ=−0.54) and p-tau181 (PCG: ρ=−0.38; LH:ρ =−0.39), as well as with lower Aβ42/40 (PCG:ρ=0.40; LH:ρ=0.32). Higher mIns/tCr was associated with higher p-tau181/Aβ42 (PCG: ρ=0.56; LH:ρ=0.46) and p-tau181 (PCG:ρ=0.37; LH:ρ=0.31). Lower PCG and LH tNAA/mIns ratios were associated with lower MMSE (PCG:ρ=0.53; LH:ρ=0.46), while higher p-tau181/Aβ42 was associated with lower MMSE (ρ=−0.49). ¹H-MRS-derived gliosis and neuronal injury biomarkers are associated with early AD pathology, and cognitive performance, supporting their use as noninvasive biomarkers in early AD.

该研究的目的是评估阿尔茨海默病（AD）血浆生物标志物与体内质子磁共振波谱（H-MRS）标志物的关系，以及它们在AD连续体早期阶段与认知功能的关系。确定这些关联可以澄清AD相关的生物学途径，并支持开发整合AD血液和H-MRS生物标志物，用于早期检测这些途径。来自梅奥诊所衰老研究的55名老年人（40名认知未受损，15名轻度认知障碍）在3T时接受了后扣带回（PCG）和左海马（LH）的单体素¹H-MRS (sLASER)，并进行了a - β42/40、磷酸化tau （p-tau181）和p-tau181/ a - β42比值的血浆检测。血浆生物标志物与H-MRS代谢物（肌醇[mIns]/总肌酸[tCr]、总n -乙酰天冬氨酸[tNAA]/tCr和tNAA/mIns）之间的关系采用调整年龄和性别的部分Spearman相关性（ρ, ρ）进行检验。接下来，对p-tau181/ a - β42和tNAA/ min与迷你精神状态检查的关联进行检查，调整相同的协变量加上教育。在PCG和LH区域，较低的tNAA/ min与较高的p-tau181/ a - β42 （PCG:ρ=−0.59;LH:ρ=−0.54）和p-tau181 （PCG:ρ=−0.38;LH:ρ=−0.39）以及较低的a - β42/40 （PCG:ρ=0.40; LH:ρ=0.32）相关。较高的min /tCr与较高的p-tau181/ a - β42 （PCG:ρ= 0.56; LH:ρ=0.46）和p-tau181 （PCG:ρ=0.37; LH:ρ=0.31）相关。较低的PCG和LH tNAA/ min比值与较低的MMSE相关（PCG:ρ=0.53; LH:ρ=0.46），而较高的p-tau181/ a - β42与较低的MMSE相关（ρ= - 0.49）。¹h - mrs衍生的神经胶质瘤和神经元损伤生物标志物与早期阿尔茨海默病病理和认知表现相关，支持它们作为早期阿尔茨海默病的无创生物标志物。

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引用次数: 0