Neurobiology of Aging最新文献_第2页

Rare ABCA7 mutations in Alzheimer’s disease and cerebral amyloid angiopathy pathology 罕见ABCA7突变在阿尔茨海默病和脑淀粉样血管病病理中的作用。

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2026-01-01 DOI: 10.1016/j.neurobiolaging.2025.12.010

Elisabeth Hendrickx Van de Craen , Liene Bossaerts , Anne Sieben , Tobi Van den Bossche , Maria Bjerke , Bernard Hanseeuw , Bruno Bergmans , Rik Vandenberghe , Peter P. De Deyn , Patrick Cras , Kristel Sleegers , Sebastiaan Engelborghs , Christine Van Broeckhoven , Julie van der Zee , BELNEU Consortium

Rare mutations in the ATP binding cassette subfamily A member 7 (ABCA7) gene are known risk factors for Alzheimer’s disease (AD). Genetic sequencing in 1372 Belgian patients previously revealed rare ABCA7 mutations in 102 carriers, 58 with a premature termination codon mutation (PTC) and 44 with a missense mutation. Among carriers, 14 received post-mortem examination. Here, we reviewed and report the demographics, clinicopathological phenotypes, and diagnoses of identified ABCA7 mutation carriers. Carriers mostly developed late-onset AD (71 ± 9 years) and had a high familial load (67 % with positive family history). Patients presented with classic amnestic AD based on neuropsychological assessment, imaging and CSF biomarkers. However, vascular involvement was observed in a considerable part of patients, leading to diagnosis of vascular dementia (9 %) and cerebral amyloid angiopathy (CAA) (6 %). In line with this, neuropathology of the 14 examined carriers uncovered extensive levels of CAA and AD hallmarks. Carriers of an ABCA7 missense mutations displayed a less aggressive phenotype, with comparable onset but longer disease duration compared to carriers of a PTC mutation. Furthermore, non-amnestic features including language, dysexecutive and behavioural symptoms, were more frequently seen in PTC patients (18 % vs 9 %), as was the case for concomitant vascular disease (22 % vs 10 %). Taken together, the clinical phenotype of rare ABCA7 mutation carriers spans the AD-CAA spectrum. Patients present with a classical AD phenotype although clinical heterogeneity is observed among carriers. The presence of a cerebrovascular component (CAA) may, in part, explain this heterogeneity.

ATP结合盒亚家族A成员7 （ABCA7）基因的罕见突变是已知的阿尔茨海默病（AD）的危险因素。对1372名比利时患者的基因测序先前显示，102名携带者中有罕见的ABCA7突变，58名携带过早终止密码子突变（PTC）， 44名携带错义突变。在携带者中，有14人接受了尸检。在这里，我们回顾并报告了已确定的ABCA7突变携带者的人口统计学、临床病理表型和诊断。携带者多为迟发性AD（71 ± 9年），家族负荷高（67 %，有阳性家族史）。根据神经心理学评估、影像学和脑脊液生物标志物，患者表现为典型的健忘性AD。然而，在相当一部分患者中观察到血管受累，导致血管性痴呆（9 %）和脑淀粉样血管病（6 %）的诊断。与此相一致的是，14名被检查的携带者的神经病理学发现了广泛水平的CAA和AD特征。ABCA7错义突变的携带者表现出较低的侵袭性表型，与PTC突变携带者相比，其发病相似，但病程较长。此外，包括语言、执行障碍和行为症状在内的非遗忘特征在PTC患者中更为常见（18 %对9 %），同时伴有血管疾病的情况也是如此（22 %对10 %）。总之，罕见的ABCA7突变携带者的临床表型跨越了AD-CAA谱。患者表现为典型的AD表型，尽管在携带者中观察到临床异质性。脑血管成分（CAA）的存在可能部分解释了这种异质性。

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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 : 2025-12-31 DOI: 10.1016/S0197-4580(25)00227-1

引用次数: 0

Resting-state EEG aperiodic exponent moderates the association between age and memory performance in older adults 静息状态脑电图非周期指数调节年龄与老年人记忆表现的关系。

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-12-24 DOI: 10.1016/j.neurobiolaging.2025.12.008

Alicia J. Campbell , Toomas Erik Anijärv , Mikael Johansson , Thomas Pace , Jim Lagopoulos , Daniel F. Hermens , Jacob M. Levenstein , Sophie C. Andrews

Memory functions are susceptible to age-related cognitive decline, making it essential to explore the underlying neurophysiological mechanisms that contribute to memory function during healthy ageing. Resting-state EEG (rsEEG) parameters, particularly the aperiodic exponent, a marker of cortical excitation-inhibition balance, and individual alpha peak frequency, a correlate of neural processing efficiency, have demonstrated associations with ageing and cognitive functions. This study investigated associations between these rsEEG markers and performance across multiple memory systems in healthy older adults (n = 99) aged 50–84 years, specifically the direct associations of these markers on memory across episodic, working, and visual short-term memory systems, assessed via computerised tasks, as well as their moderating effects on age-memory relationships. While no direct associations were seen between rsEEG markers and memory performance across tasks beyond the contribution of age, gender and education, results revealed significant moderating effects of the aperiodic exponent on age-related performance in episodic and visual short-term memory. Notably, for individuals with a higher exponent, age was not significantly associated with episodic or visual short-term memory performance, whereas those with average and lower exponent values showed poorer performance with older age. These findings suggest that average and lower aperiodic exponents may reflect a marker of decrement in age-related memory performance and higher exponents may index an underlying protective mechanism against age-related memory decline. This investigation extends the current understanding of cognitive ageing mechanisms by identifying the aperiodic exponent as a potential biomarker explaining individual differences in cognitive ageing trajectories in older adult populations, particularly in episodic and visual short-term memory systems, and establishes a framework for studying neuroprotective mechanisms and developing interventions to preserve cognitive function in older adults.

记忆功能容易受到与年龄相关的认知衰退的影响，因此探索健康衰老过程中影响记忆功能的潜在神经生理机制至关重要。静息状态脑电图（rsEEG）参数，特别是非周期指数（皮质兴奋-抑制平衡的标志）和个体α峰频率（神经处理效率的相关指标），已被证明与衰老和认知功能有关。本研究调查了50-84岁健康老年人（n = 99）中这些rsEEG标记与多个记忆系统表现之间的关联，特别是这些标记与情景、工作和视觉短期记忆系统之间的直接关联，通过计算机化任务进行评估，以及它们对年龄-记忆关系的调节作用。虽然除了年龄、性别和教育程度的影响外，rsEEG标记与记忆表现之间没有直接联系，但结果显示，非周期性指数对情景和视觉短期记忆中与年龄相关的表现有显著的调节作用。值得注意的是，对于指数较高的个体，年龄与情景或视觉短期记忆的表现没有显著相关性，而指数平均值和较低的个体随着年龄的增长表现出较差的表现。这些发现表明，平均和较低的非周期指数可能反映了与年龄相关的记忆性能下降的标志，而较高的指数可能反映了与年龄相关的记忆衰退的潜在保护机制。本研究通过确定非周期指数作为一种潜在的生物标志物来解释老年人认知衰老轨迹的个体差异，特别是在情景和视觉短期记忆系统中，扩展了目前对认知衰老机制的理解，并为研究神经保护机制和开发保护老年人认知功能的干预措施建立了框架。

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引用次数: 0

Neuronal TrkB supports adult cortical oligodendrogenesis in the brains of older adult mice 神经元TrkB支持成年小鼠大脑皮层少突胶质形成。

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-12-24 DOI: 10.1016/j.neurobiolaging.2025.12.009

Madeline Nicholson , Rhiannon J. Wood , Simon S. Murray , Jessica L. Fletcher

Lifelong oligodendrogenesis and myelination is critical for healthy brain aging. Using cumulative labelling with thymidine analogue, 5-ethynyl-2’-deoxyuridine (EdU) for 6-weeks commencing at 2-, 12- and 18-months of age in C57BL/6 mice, we found that oligodendrocyte progenitor cell (OPC) proliferation and oligodendroglial densities are relatively stable in the adult mouse optic nerve, corpus callosum and somatosensory cortex. We also found that more proliferative adult OPCs differentiate into oligodendrocytes in the somatosensory cortex than the corpus callosum during aging. To determine the role of neuronal TrkB in adult oligodendrogenesis in the older brain, we generated Thy1-CreER^T2-EYFP::TrkB^fl/fl mice and administered tamoxifen at 12-months of age, before cumulative EdU labelling. This resulted in TrkB deletion from 10 % of layer V projection neurons in the somatosensory cortex and reduced the level of TrkB in the remaining Thy1-YFP⁺ neurons by approximately half. Neuronal TrkB reduction had no effect on OPC proliferation in the optic nerve, corpus callosum or somatosensory cortex. However, there was a significant decrease in the proportion of proliferative OPCs that contributed to the post-mitotic oligodendrocyte population in the somatosensory cortex 5-months later. These findings provide insight into regional and age-related changes in oligodendroglial population dynamics and identify that neuronal TrkB supports cortical oligodendrogenesis during healthy brain aging.

终生少突胶质形成和髓鞘形成对健康的大脑衰老至关重要。从2、12和18月龄开始，用胸腺嘧啶类似物5-乙基-2′-脱氧尿苷（EdU）对C57BL/6小鼠进行6周的累积标记，我们发现成年小鼠视神经、胼胝体和体感觉皮层中少突胶质细胞祖细胞（OPC）的增殖和少突胶质细胞密度相对稳定。我们还发现，随着年龄的增长，更多增生的成年OPCs在体感觉皮层分化为少突胶质细胞，而不是胼胝体。为了确定神经元TrkB在老年大脑成人少突胶质发生中的作用，我们制造了Thy1-CreERT2-EYFP::TrkBfl/fl小鼠，并在12月龄时给予他莫昔芬，然后进行累积EdU标记。这导致10 %的体感觉皮层V层投射神经元的TrkB缺失，其余Thy1-YFP+神经元的TrkB水平降低了约一半。神经元TrkB减少对视神经、胼胝体和体感觉皮层的OPC增殖无影响。然而，5个月后，在体感觉皮层中，促进有丝分裂后少突胶质细胞群的增殖性OPCs的比例显著下降。这些发现提供了对少突胶质种群动态的区域和年龄相关变化的见解，并确定了在健康大脑衰老过程中神经元TrkB支持皮层少突胶质发生。

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引用次数: 0

Regional growth rates of white matter hyperintensities are associated with beta-amyloid burden 白质高信号的局部生长速率与β -淀粉样蛋白负荷有关

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-12-19 DOI: 10.1016/j.neurobiolaging.2025.12.006

Jeremy F. Strain , Maryam Rahmani , Chia-Ling Phuah , Donna Dierker , Jingqin Luo , Christopher Owen , Andrei G. Vlassenko , Hussain Jafri , Pierreck Bourgeat , Jurgen Fripp , Liang Jin , Krista Moulder , Tammie Benzinger , Chengjie Xiong , Jin-Moo Lee , Michael Weiner , Colin L. Masters , John C. Morris , Kyle Womack , Manu S. Goyal

There is increasing evidence for an association between white matter hyperintensities (WMH) and brain beta-amyloid deposition. How WMH are longitudinally associated with brain beta-amyloid burden requires further investigation, particularly with respect to co-existent vascular risk factors and differences across white matter regions. We measured WMH on MRI and vascular risk factors in a combined neuroimaging data set of cognitively normal and individuals with dementia comprised of the ADNI, AIBL and OASIS3 studies, which includes harmonized centiloid estimates of beta-amyloid burden from PET imaging. WMH were measured using the TrUE-Net algorithm. Vascular risk factors were extracted from provided clinical data and used to calculate individual revised Framingham Stroke Risk Profile (FSRP) scores. Linear mixed effects modelling was used to determine the relationship between the growth rate of WMH and baseline beta-amyloid burden, controlling for age, sex, APOE4 status, and vascular risk factors. 1243 participants [49 % female, mean age 71.7 y (SD 7.6 y)] had at least 3 brain MRIs. Linear mixed models demonstrate robust independent cross-sectional relationships between WMH and baseline beta-amyloid burden (beta coefficient=0.27, p < 0.001), age (beta coefficient=0.04, p < 0.001) and vascular risk factors (beta coefficient=0.25, p < 0.001). Growth rates of WMH increased with baseline beta-amyloid burden (slope=0.021, p < 0.001) and decreased with anti-hypertensive medications (slope=-0.019, p = 0.002), above and beyond age, APOE4 status, and other vascular risk factors. The longitudinal association for beta-amyloid burden persisted in a similar analysis for parietal WM. Our study suggests that in Alzheimer disease research cohorts, WMH progression is associated with age and beta-amyloid burden, particularly in parietal white matter, and slowed by anti-hypertensive treatment.

越来越多的证据表明白质高信号（WMH）与大脑β -淀粉样蛋白沉积之间存在关联。WMH与脑β -淀粉样蛋白负担的纵向关系需要进一步研究，特别是关于共存的血管危险因素和白质区域的差异。我们在由ADNI、AIBL和OASIS3研究组成的认知正常和痴呆个体的联合神经影像学数据集中测量了MRI上的WMH和血管危险因素，其中包括PET成像对β -淀粉样蛋白负荷的统一centiloid估计。采用TrUE-Net算法测量WMH。从提供的临床数据中提取血管危险因素，并用于计算个人修订的Framingham卒中风险概况（FSRP）评分。在控制年龄、性别、APOE4状态和血管危险因素的情况下，采用线性混合效应模型确定WMH生长速率与基线β -淀粉样蛋白负荷之间的关系。1243名参与者[49 %为女性，平均年龄71.7岁（SD 7.6岁）]进行了至少3次脑mri检查。线性混合模型显示，WMH与基线β -淀粉样蛋白负荷（β系数=0.27,p <； 0.001）、年龄（β系数=0.04,p <； 0.001）和血管危险因素（β系数=0.25,p <； 0.001）之间存在强大的独立横断面关系。WMH的生长速率随基线β -淀粉样蛋白负荷（斜率=0.021,p <； 0.001）而增加，随抗高血压药物（斜率=-0.019,p = 0.002）、年龄、APOE4状态和其他血管危险因素而下降。在一个类似的顶叶性脑白质分析中，β -淀粉样蛋白负荷的纵向关联仍然存在。我们的研究表明，在阿尔茨海默病研究队列中，WMH的进展与年龄和β -淀粉样蛋白负荷有关，特别是在顶叶白质中，并通过抗高血压治疗减缓。

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引用次数: 0

Diagnostic performance of plasma pTau217/Aβ42 ratio and a three-zone threshold model for Alzheimer’s disease 血浆pTau217/ a - β42比值及三区阈值模型对阿尔茨海默病的诊断价值

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-12-18 DOI: 10.1016/j.neurobiolaging.2025.12.005

Alberto Benussi , Marco Michelutti , Tiziana Maria Isabella Lombardo , Barbara Toffoletto , Federica Palacino , Valentina Cenacchi , Luca Pelusi , Francesco Capacchione , Alina Menichelli , Alberto Perego , Francesca Sirianni , Tatiana Cattaruzza , Paolo Manganotti

Early and accurate diagnosis of Alzheimer’s disease (AD) typically relies on invasive or expensive methods like cerebrospinal fluid (CSF) biomarkers and amyloid PET imaging. Blood-based biomarkers, particularly plasma phosphorylated tau (pTau₁₈₁, pTau₂₁₇) and amyloid-beta ratios (Aβ₄₂/₄₀), offer a more accessible diagnostic alternative. This study assessed the diagnostic accuracy of plasma biomarkers and developed a three-zone classification model to reduce reliance on invasive confirmatory tests. We retrospectively evaluated 109 participants referred to a tertiary memory clinic. Participants underwent cognitive assessments, brain MRI, CSF biomarker analyses (pTau₁₈₁, Aβ₄₂/₄₀), and plasma biomarker measurements (pTau₁₈₁, pTau₂₁₇, Aβ₄₂/₄₀, pTau₂₁₇/Aβ₄₂ ratio). Diagnostic performance was evaluated using ROC analyses, and thresholds achieving ≥ 95 % sensitivity and specificity were used to define low, intermediate and high-risk zones. Plasma biomarkers correlated significantly with CSF biomarkers. For identifying AD pathology (A+/T + vs. others), plasma pTau₂₁₇ and the pTau₂₁₇/Aβ₄₂ ratio demonstrated the highest accuracy (both AUC=0.95), outperforming plasma pTau₁₈₁ (AUC=0.88) and Aβ₄₂/₄₀ ratio (AUC=0.73). At optimal thresholds, plasma pTau₂₁₇ showed 87.5 % sensitivity and 93.4 % specificity, whereas the pTau₂₁₇/Aβ₄₂ ratio showed higher sensitivity (95.8 %) but lower specificity (85.2 %). Using the three-zone model, plasma pTau₂₁₇ enabled definitive classification in 80.7 % of patients, increasing to 84.4 % with the pTau₂₁₇/Aβ₄₂ ratio. Among patients with mild cognitive impairment, plasma pTau₂₁₇ achieved excellent accuracy (AUC=0.98). Plasma pTau₂₁₇, alone or combined with Aβ₄₂, provides highly accurate and scalable identification of AD pathology, substantially reducing the need for invasive diagnostic procedures.

阿尔茨海默病（AD）的早期和准确诊断通常依赖于侵入性或昂贵的方法，如脑脊液（CSF）生物标志物和淀粉样蛋白PET成像。基于血液的生物标志物，特别是血浆磷酸化tau蛋白（pTau181, pTau217）和淀粉样蛋白- β比率（a - β42/40），提供了更容易获得的诊断选择。本研究评估了血浆生物标志物的诊断准确性，并建立了一个三区分类模型，以减少对侵入性确证试验的依赖。我们回顾性地评估了109名转诊至第三记忆诊所的参与者。参与者接受认知评估、脑MRI、CSF生物标志物分析（pTau181、a - β42/40）和血浆生物标志物测量（pTau181、pTau217、a - β42/40、pTau217/ a - β42比值）。采用ROC分析评估诊断效果，并采用≥ 95 %的敏感性和特异性阈值来定义低、中、高风险区域。血浆生物标志物与脑脊液生物标志物显著相关。鉴别AD病理(A+/T + vs.；血浆pTau217和pTau217/ a - β42比值的准确度最高（AUC均为0.95），优于血浆pTau181 （AUC=0.88）和a - β42/40比值（AUC=0.73）。在最佳阈值下，血浆pTau217的敏感性为87.5 %，特异性为93.4 %，而pTau217/ a - β42的敏感性较高（95.8% %），特异性较低（85.2% %）。使用三区模型，血浆pTau217使80.7% %的患者能够明确分类，随着pTau217/ a - β42的比例增加到84.4 %。在轻度认知障碍患者中，血浆pTau217的准确性非常好（AUC=0.98）。血浆pTau217，单独或联合Aβ42，提供了高度准确和可扩展的阿尔茨海默病病理鉴定，大大减少了侵入性诊断程序的需要。

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引用次数: 0

Cognitive reserve is associated with less cognitive decline from white matter hyperintensities 认知储备与较少由白质高强度引起的认知衰退有关

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-12-16 DOI: 10.1016/j.neurobiolaging.2025.12.004

Arthur P. Hamilton , Kaiah N. Sotebeer , John G. Grundy , Katherine Chadwick , Cassandra Morrison , Mahsa Dadar , Ellen Bialystok , John A.E. Anderson , for the Alzheimer’s Disease Metabolomics Consortium

Previous research examining the contribution of white matter hyperintensities (WMHs) to cognitive decline has focused on overall lesion burden. A new approach, afforded by the Lesion Quantification Toolkit (LQT), measures localized connectivity disruption from WMHs to better estimate their impact on cognition. This methodology shifts the focus from lesion volume to the level of network disruption between brain regions. In this novel study, we applied the LQT approach to healthy aging and linked the degree of disconnection of gray matter by WMHs to both cognitive impairment and resilience via cognitive reserve. Using three pre-existing MRI datasets of older adults (total N = 259), we used the LQT to examine localized disruptions to brain connectivity due to WMHs. We then used partial least-squares path modeling to examine the relationships between this disruption, cognitive performance, age, and cognitive reserve. The results support a link between connectivity disruption and reduced cognitive performance. Results from all three individual datasets, one of which included a detailed measure of cognitive reserve, showed a link between cognitive reserve and higher cognitive performance, suggesting cognitive reserve allows for maintained cognitive function in spite of the negative impact of WMHs.

先前研究白质高强度（WMHs）对认知能力下降的贡献主要集中在总体病变负担上。病变量化工具包（LQT）提供了一种新的方法，测量wmh的局部连接中断，以更好地估计它们对认知的影响。这种方法将焦点从病变体积转移到大脑区域之间网络中断的水平。在这项新颖的研究中，我们将LQT方法应用于健康衰老，并将WMHs的灰质断开程度与认知障碍和认知储备的恢复力联系起来。使用三个预先存在的老年人MRI数据集（总N = 259），我们使用LQT来检查由于wmh引起的局部脑连接中断。然后，我们使用偏最小二乘路径模型来检查这种中断、认知表现、年龄和认知储备之间的关系。研究结果支持连接中断和认知能力下降之间的联系。所有三个单独的数据集的结果，其中一个包括认知储备的详细测量，显示了认知储备与更高的认知表现之间的联系，表明认知储备允许维持认知功能，尽管WMHs的负面影响。

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引用次数: 0

Excess iron may accelerate amyloid beta accumulation in the brains of older mice 过量的铁可能会加速老年小鼠大脑中淀粉样蛋白的积累。

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-12-13 DOI: 10.1016/j.neurobiolaging.2025.12.003

Soo-Jin Song, Jung-A Shin

Aging is a natural physiological process that may be accompanied by pathological changes, particularly in the brain. Iron is an essential trace element supporting various physiological functions and maintaining cellular homeostasis. However, iron levels tend to increase in certain brain regions of older adults and are associated with the development of neurodegenerative diseases. Despite this association, the causal relationship between aging, iron accumulation, and neurodegenerative diseases remains unknown. This study aimed to elucidate the potential contribution of systemic iron overload (IO) to brain pathology during aging. An IO model was established by intraperitoneal iron dextran (0.5 g/kg), 5 days/week for 4 weeks into C57BL/6 mice. Animals were divided into control and IO groups and further categorized into younger and older mice. No parenchymal iron accumulation was observed in any group; however, ferritin expression increased with IO and showed as plaques in older mice regardless of IO. Amyloid beta (Aβ) aggregation was observed in the entorhinal cortex and hippocampus, with higher burden in the older IO group. Ferritin plaques localized to the same regions as Aβ aggregation, and both showed a marked increase in older IO mice. The hippocampal Aβ 42/40 ratio was also increased in this group. Additionally, excessive iron was associated with reduced exploratory activity and showed trends toward impaired spatial working memory in older mice. These findings suggest that while aging is not pathological, IO may accelerate Aβ pathology during aging, although the presence of such pathology does not necessarily indicate neurodegeneration or cognitive impairment.

衰老是一种自然的生理过程，可能伴随着病理变化，特别是在大脑中。铁是一种必需的微量元素，支持多种生理功能和维持细胞内稳态。然而，老年人大脑某些区域的铁含量往往会增加，并与神经退行性疾病的发展有关。尽管存在这种关联，但衰老、铁积累和神经退行性疾病之间的因果关系仍不清楚。本研究旨在阐明系统性铁超载（IO）在衰老过程中对脑病理的潜在贡献。采用右旋糖酐铁（0.5 g/kg）腹腔注射C57BL/6小鼠，5天/周，连续4周建立IO模型。动物分为对照组和IO组，并进一步分为年轻组和老年组。各组均未见实质铁积累；然而，铁蛋白的表达随着IO的增加而增加，并且在老年小鼠中表现为斑块，而与IO无关。β -淀粉样蛋白（Aβ）聚集于内嗅皮层和海马，且年龄较大的IO组负担更重。铁蛋白斑块定位于与a β聚集相同的区域，并且在老年IO小鼠中两者都显着增加。海马Aβ 42/40比值升高。此外，过量的铁与探索活动减少有关，并显示出老年小鼠空间工作记忆受损的趋势。这些发现表明，虽然衰老不是病理性的，但IO可能会加速衰老过程中的Aβ病理，尽管这种病理的存在并不一定表明神经退行性变或认知障碍。

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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 : 2025-12-06 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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