Are oligodendrocytes the missing link in Alzheimer’s disease and related dementia research?,Molecular Neurodegeneration

当前位置： X-MOL 学术 › Mol. Neurodegener. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Are oligodendrocytes the missing link in Alzheimer’s disease and related dementia research?
Molecular Neurodegeneration ( IF 14.9 ) Pub Date : 2024-11-17 , DOI: 10.1186/s13024-024-00760-6
Sharyn L. Rossi, Diane E. Bovenkamp

Oligodendrocytes (OLs) and their lineage progenitor (OPCs) and precursor cells are widely studied and recognized as promising therapeutic targets for multiple neurodegenerative diseases and disorders including multiple sclerosis, spinal cord injuries, traumatic brain injuries, stroke, Parkinson’s disease, ALS, and others. Yet, their role in Alzheimer’s disease and related dementias (ADRDs), despite their complex, multi-factorial nature, remains largely underappreciated and understudied. Mounting evidence supports the role of oligodendrocyte dysfunction in ADRD which begins with their normal homeostatic role during development and non-disease physiological states.

During development, OPCs follow an intricate temporal and spatial pattern as they migrate, proliferate, and differentiate into the myelinating cells of the CNS. While migrating, pools of oligodendrocyte precursor cells and OPCs are distributed throughout the brain and spinal cord. OLs and OPCs release growth factors that play a role in synaptic transmission and participate in synaptic engulfment and remodeling [1]. OPCs are a heterogenous subtype that persist into adulthood and have various (originally considered atypical) functions including neuromodulation through direct synaptic connections with neurons, vascularization and angiogenesis, coordinated interactions with astrocytes in the development and maintenance of the blood brain barrier, and immunomodulatory properties through interactions with microglia. OPCs play a critical role in synaptic remodeling, circuit plasticity, and regenerative mechanisms, proliferating and differentiating in response to an insult or injury. Activated OPCs can undergo oligodendrogenesis to form fully functional mature OLs that participate in the remyelination of disconnected or dysfunctional brain circuits but have also been shown to differentiate into astrocytes and neurons [2]. These responses and functions are tightly controlled by numerous signaling pathways, including Notch and PI3/Akt pathways, that are known to be dysregulated in ADRD [3].

Mature myelin forming OLs are made primarily of lipids and cholesterol and control information processing speed across local neuronal circuits and distal targets using precise modulation to serve appropriate biological functions. As myelination occurs throughout development and into adulthood, the process is heavily influenced by personal experience, lifestyle, and other exposures (the exposome) that modify the transcriptomic signatures of OPCs and OLs. Dynamic shifts in myelin sheath thickness and in the location of nodes of Ranvier (junctions between myelin segments) control information flow and facilitate synchrony between and across neural networks. These networks are required for learning and memory and experience-dependent myelin formation facilitates memory consolidation and recall [4]. In addition to controlling neural activity, OLs provide metabolic support for neurons [5] and interact with microglia and astrocytes to control lipid metabolism, extracellular matrix dynamics, and immune responses [6, 7].

Dysregulation of these OL functions has been implicated in the progression of ADRD and neuroimaging studies have confirmed global changes in myelin integrity for decades. More recently, high profile studies in humans have provided irrefutable evidence that OLs play an integral role in the progression and possibly even the onset of ADRD. SMOC1 is a protein recently discovered in the CSF of people with autosomal dominant AD decades before symptom onset [8]. SMOC1 is almost exclusively expressed in OPCs and OLs in the brain (Single cell type - SMOC1 - The Human Protein Atlas https://www.proteinatlas.org/ENSG00000198732-SMOC1/single+cell+type) and has been implicated in the failure of oligodendrogenesis in Spinocerebellar Ataxia [9]. Furthermore, APOE4, the major risk factor for AD, causes the aberrant deposition of cholesterol in OLs, impairing myelin maintenance and function [10]. Dysfunctional oligodendrogenesis and remyelination in ADRD is likely driven by disease associated transcriptomic changes and the conversion of OPCs and OLs to senescent phenotypes [11]. OLs also contribute and respond to amyloidosis in AD as they accumulate around amyloid plaques, express genes associated with amyloid production [12], and even contribute to amyloid deposition [13, 14]. Perhaps most intriguing is new data released by the Allen Institute showing two AD-associated phases of pathology in postmortem tissue. The first stage consists of loss of myelinating oligodendrocytes and a selectively vulnerable population of somatostatin interneurons which is accompanied by an upregulation of remyelination programs in OPCs that ultimately fail. These findings indicate that OLs are involved at the earliest stages of disease progression, before symptom onset and accumulation of toxic proteins in AD [15].

At a time when the ADRD field is reflecting on “All the Alzheimer’s Research We Didn’t Do” (Piller C. Opinion, https://www.nytimes.com/2024/07/07/opinion/alzheimers-missed-opportunities.html), it is crucial to ensure we anticipate and address any potential pitfalls or gaps as we move forward as a field. Including OLs in ADRD research, particularly in ongoing big data efforts, is essential for a comprehensive understanding of these diseases. Invaluable resources that aim to extensively characterize cell types across various systems and neurodegenerative diseases would lack a fundamental cellular variable whose homeostatic biological functions are inevitably perturbed by the ADRD associated milieu.

It is essential for all researchers focused on ADRD to recognize the significant role OLs and oligodendrogenesis play in neurodegeneration, plasticity, and repair. As key players in maintaining axonal health, modulating synaptic plasticity, and supporting the structural integrity of neuronal circuits, OLs are a suitable and viable therapeutic target for ADRD (Fig. 1). Cross-disease learnings from other neurodegenerative fields can provide valuable insights into the therapeutic potential of OLs and OPCs that can serve as a foundation for advancing ADRD research. Various clinical trials for MS and ALS are aimed at restoring myelin by activating endogenous OPCs, modulating neuroinflammation to create a more conducive remyelination environment, and/or through exogenous transplantation of various stem and progenitor cell populations [16]. Considering these cells as both drivers and modifiers of ADRD pathology will fill knowledge gaps and open new treatment avenues, including targeted senolytics, gene editing, and harnessing the proliferative and differentiation potential of OPCs through noninvasive interventions like focused ultrasound and transcranial magnetic stimulation and possibly even directed differentiation via in situ conversion.

In the last decade, ADRD research has experienced a significant shift toward viewing and studying dementia through a multisystem holistic lens. Despite multiple reports identifying oligodendrocytes as key mediators of pathological processes in humans and animal models, their full contributions to disease mechanisms and potential as disease modifiers has not been realized. Increased interest in the role OLs play in ADRD can be fueled by increased funding and initiatives focused on oligodendroglial interactions with cell types vulnerable to ADRD pathology. Apparent action items for government, for profit and not for profit funders to include OLs and OPCs in ADRD research could include:

1.
Requests that OLs and OPCs be added to all currently active and future initiations of multi-cellular ‘omics,’ systems biology, circuit networks, AI/deep learning, and other techniques/databases to better understand neurodegenerative disease for all organisms, but especially for those studies looking to better understand ADRD risk and progression in humans.
2.
Addition of OL and OPC biomarkers to molecular panels researching basic, translational and clinical diagnostic, prognostic and treatment studies in people affected by various ADRD.
3.
Addition of OL and OPC biomarkers to systems biology, in situ and in vivo characterization of animal and cellular models of ADRD.
4.
ADRD funding agencies should seek out and prioritize projects that include OLs and/or OPCs in their scientific or therapeutic approach. The inclusion of OLs should be strongly considered in large-scale data collection initiatives that compare and contrast cell types involved in ADRD.

N/A.

OL:: Oligodendrocyte
OPC:: Oligodendrocyte Progenitor Cell
ADRD:: Alzheimer’s Disease and Related Dementias

Auguste YSS, Ferro A, Kahng JA, Xavier AM, Dixon JR, Vrudhula U, et al. Oligodendrocyte precursor cells engulf synapses during circuit remodeling in mice. Nat Neurosci. 2022;25:1273–8.
Article CAS PubMed PubMed Central Google Scholar
Akay LA, Effenberger AH, Tsai L-H. Cell of all trades: oligodendrocyte precursor cells in synaptic, vascular, and immune function. Genes Dev. 2021;35:180–98.
Article CAS PubMed PubMed Central Google Scholar
Hirschfeld LR, Risacher SL, Nho K, Saykin AJ. Myelin repair in Alzheimer’s disease: a review of biological pathways and potential therapeutics. Transl Neurodegener. 2022;11:47.
Article CAS PubMed PubMed Central Google Scholar
Fields RD, Bukalo O. Myelin makes memories. Nat Neurosci. 2020;23:469–70.
Article CAS PubMed PubMed Central Google Scholar
Philips T, Rothstein JD. Oligodendroglia: metabolic supporters of neurons. J Clin Invest. 2017;127:3271–80.
Article PubMed PubMed Central Google Scholar
Marangon D, Boccazzi M, Lecca D, Fumagalli M. Regulation of oligodendrocyte functions: targeting lipid metabolism and extracellular matrix for myelin repair. J Clin Med. 2020;9:470.
Article CAS PubMed PubMed Central Google Scholar
Peferoen L, Kipp M, Valk P, Noort JM, Amor S. Oligodendrocyte-microglia cross-talk in the central nervous system. Immunology. 2014;141:302–13.
Article CAS PubMed PubMed Central Google Scholar
Johnson ECB, Bian S, Haque RU, Carter EK, Watson CM, Gordon BA, et al. Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease. Nat Med. 2023;29:1979–88.
Article CAS PubMed PubMed Central Google Scholar
Schuster KH, Zalon AJ, Zhang H, DiFranco DM, Stec NR, Haque Z, et al. Impaired oligodendrocyte maturation is an early feature in SCA3 Disease Pathogenesis. J Neurosci. 2022;42:1604–17.
Article CAS PubMed PubMed Central Google Scholar
Blanchard JW, Akay LA, Davila-Velderrain J, von Maydell D, Mathys H, Davidson SM, et al. APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes. Nature. 2022;611:769–79.
Article CAS PubMed PubMed Central Google Scholar
Schlett JS, Mettang M, Skaf A, Schweizer P, Errerd A, Mulugeta EA, et al. NF-κB is a critical mediator of post-mitotic senescence in oligodendrocytes and subsequent white matter loss. Mol Neurodegener. 2023;18:24.
Article CAS PubMed PubMed Central Google Scholar
Gazestani V, Kamath T, Nadaf NM, Dougalis A, Burris SJ, Rooney B, et al. Early Alzheimer’s disease pathology in human cortex involves transient cell states. Cell. 2023;186:4438–e445323.
Article CAS PubMed PubMed Central Google Scholar
Sasmita AO, Depp C, Nazarenko T, Sun T, Siems SB, Ong EC, et al. Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice. Nat Neurosci. 2024;27:1668–74.
Article CAS PubMed PubMed Central Google Scholar
Akihiro I, Pathoulas JA, Omar OM, Fathy, Ge, Yingying, Yao, Annie Y, Pantalena, Tressa et al. Contribution of amyloid deposition from oligodendrocytes in a mouse model of Alzheimer’s disease. Mol Neurodegener. 2024; https://doi.org/10.1186/s13024-024-00759-z.
Gabitto MI, Travaglini KJ, Rachleff VM et al. Integrated multimodal cell atlas of Alzheimer’s disease. Nat Neurosci. 2024; https://doi.org/10.1038/s41593-024-01774-5.
Parrilla GE, Gupta V, Wall RV, Salkar A, Basavarajappa D, Mirzaei M, et al. The role of myelin in neurodegeneration: implications for drug targets and neuroprotection strategies. Rev Neurosci. 2024;35:271–92.
Article CAS PubMed Google Scholar

Download references

As always, thank you to the dedicated donors supporting Alzheimer’s Disease Research, a BrightFocus Foundation program.

Authors and Affiliations

BrightFocus Foundation, 22512 Gateway Center Drive, Clarksburg, MD, 20871, USA
Sharyn L. Rossi & Diane E. Bovenkamp

Authors

Sharyn L. RossiView author publications
You can also search for this author in PubMed Google Scholar
Diane E. BovenkampView author publications
You can also search for this author in PubMed Google Scholar

Contributions

SLR conceived of the work and wrote the initial draft with contributions from DEB.

Corresponding author

Correspondence to Sharyn L. Rossi.

Competing interests

SLR and DEB have no financial or non-financial competing interests related to this perspective.

Ethic approval

N/A.

Consent

N/A.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

Cite this article

Rossi, S.L., Bovenkamp, D.E. Are oligodendrocytes the missing link in Alzheimer’s disease and related dementia research?. Mol Neurodegeneration 19, 84 (2024). https://doi.org/10.1186/s13024-024-00760-6

Download citation

Received: 06 August 2024
Accepted: 02 October 2024
Published: 17 November 2024
DOI: https://doi.org/10.1186/s13024-024-00760-6

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

中文翻译：

少突胶质细胞是阿尔茨海默病和相关痴呆研究中缺失的一环吗？

少突胶质细胞（OL）及其谱系祖细胞（OPC）和前体细胞被广泛研究，并被认为是多种神经退行性疾病和病症的有前途的治疗靶点，包括多发性硬化症、脊髓损伤、创伤性脑损伤、中风、帕金森病、ALS 等。然而，尽管它们在阿尔茨海默病和相关痴呆症（ADRD）中的作用复杂、多因素，但在很大程度上仍然没有得到充分认识和研究。越来越多的证据支持少突胶质细胞功能障碍在 ADRD 中的作用，这始于它们在发育和非疾病生理状态期间的正常稳态作用。

在发育过程中，OPC 在迁移、增殖和分化为 CNS 的髓鞘细胞时遵循复杂的时间和空间模式。在迁移过程中，少突胶质细胞前体细胞和 OPC 池分布在整个大脑和脊髓中。OL 和 OPC 释放生长因子，这些生长因子在突触传递中发挥作用，并参与突触吞噬和重塑 [1]。OPC 是一种异质性亚型，持续到成年期，具有各种（最初被认为是非典型的）功能，包括通过与神经元的直接突触连接进行神经调控、血管形成和血管生成、在血脑屏障的发育和维持中与星形胶质细胞的协调相互作用，以及通过与小胶质细胞相互作用的免疫调节特性。OPC 在突触重塑、回路可塑性和再生机制中起关键作用，在损伤或损伤后增殖和分化。激活的 OPC 可以经历少突胶质生成以形成功能齐全的成熟 OL，这些 OL 参与断开连接或功能失调的大脑回路的髓鞘再生，但也已被证明可以分化为星形胶质细胞和神经元 [2]。这些反应和功能受到许多信号通路的严格控制，包括 Notch 和 PI3/Akt 通路，这些通路已知在 ADRD 中失调 [3]。

形成成熟髓鞘的 OL 主要由脂质和胆固醇组成，并使用精确调节来控制局部神经元回路和远端靶标的信息处理速度，以服务于适当的生物学功能。由于髓鞘形成发生在整个发育过程中，一直持续到成年期，因此该过程在很大程度上受到个人经历、生活方式和其他暴露（暴露组）的影响，这些暴露会改变 OPC 和 OL 的转录组特征。髓鞘厚度和 Ranvier 节点位置（髓鞘段之间的连接）的动态变化控制信息流并促进神经网络之间和神经网络之间的同步。这些网络是学习和记忆所必需的，而经验依赖性的髓鞘形成有助于记忆巩固和回忆 [4]。除了控制神经活动外，OL 还为神经元提供代谢支持 [5]，并与小胶质细胞和星形胶质细胞相互作用以控制脂质代谢、细胞外基质动力学和免疫反应 [6， 7]。

这些 OL 功能的失调与 ADRD 的进展有关，神经影像学研究证实了几十年来髓鞘完整性的整体变化。最近，备受瞩目的人类研究提供了无可辩驳的证据，表明 OLs 在 ADRD 的进展甚至可能发病中起着不可或缺的作用。SMOC1 是最近在常染色体显性遗传 AD 患者的脑脊液中发现的一种蛋白质，在症状出现前几十年 [8]。SMOC1 几乎仅在大脑的 OPC 和 OL 中表达（单细胞型 - SMOC1 - 人类蛋白质图谱 https://www.proteinatlas.org/ENSG00000198732-SMOC1/single+cell+type），并且与脊髓小脑性共济失调的少突胶质生成失败有关[9]。此外，APOE4 是 AD 的主要危险因素，会导致胆固醇在 OL 中异常沉积，从而损害髓鞘的维持和功能 [10]。ADRD 中功能失调的少突胶质生成和髓鞘再生可能是由疾病相关的转录组变化以及 OPC 和 OL 向衰老表型的转化驱动的 [11]。OL 也会导致 AD 中的淀粉样变性并对其做出反应，因为它们在淀粉样蛋白斑块周围积累，表达与淀粉样蛋白产生相关的基因 [12]，甚至有助于淀粉样蛋白沉积 [13， 14]。也许最有趣的是艾伦研究所发布的新数据，该数据显示了死后组织中与 AD 相关的两个病理阶段。第一阶段包括髓鞘少突胶质细胞的丢失和选择性脆弱的生长抑素中间神经元群，这伴随着 OPC 中髓鞘再生程序的上调，最终失败。这些发现表明，OLs 参与疾病进展的最早阶段，即 AD 症状出现和毒性蛋白积累之前 [15]。

当 ADRD 领域正在反思“我们没有做的所有阿尔茨海默病研究”（Piller C. Opinion，https://www.nytimes.com/2024/07/07/opinion/alzheimers-missed-opportunities.html 年）时，确保我们作为一个领域向前发展时预测并解决任何潜在的陷阱或差距至关重要。将 OLs 纳入 ADRD 研究，尤其是在正在进行的大数据工作中，对于全面了解这些疾病至关重要。旨在广泛表征各种系统和神经退行性疾病的细胞类型的宝贵资源将缺乏一个基本的细胞变量，其稳态生物功能不可避免地受到 ADRD 相关环境的干扰。

所有专注于 ADRD 的研究人员都必须认识到 OL 和少突生成在神经退行性变、可塑性和修复中的重要作用。作为维持轴突健康、调节突触可塑性和支持神经元回路结构完整性的关键参与者，OL 是 ADRD 的合适且可行的治疗靶点（图 1）。来自其他神经退行性领域的跨疾病学习可以为 OLs 和 OPC 的治疗潜力提供有价值的见解，这些可以作为推进 ADRD 研究的基础。MS 和 ALS 的各种临床试验旨在通过激活内源性 OPC、调节神经炎症以创造更有利的髓鞘再生环境和/或通过各种干细胞和祖细胞群的外源移植来恢复髓鞘 [16]。将这些细胞视为 ADRD 病理学的驱动因素和修饰因素将填补知识空白并开辟新的治疗途径，包括靶向溶解、基因编辑，以及通过聚焦超声和经颅磁刺激等无创干预利用 OPC 的增殖和分化潜力，甚至可能通过原位转化进行定向分化。

在过去的十年中，ADRD 研究经历了重大转变，转向通过多系统整体视角来看待和研究痴呆。尽管多篇报道确定少突胶质细胞是人类和动物模型中病理过程的关键介质，但它们对疾病机制的全部贡献和作为疾病调节剂的潜力尚未实现。增加资金和专注于少突胶质细胞与易受 ADRD 病理影响的细胞类型的相互作用的举措可以推动人们对 OL 在 ADRD 中的作用的兴趣增加。政府、营利性和非营利性资助者在 ADRD 研究中包括 OL 和 OPC 的明显行动项目可能包括：

1.

要求将 OL 和 OPC 添加到多细胞“组学”、系统生物学、电路网络、人工智能/深度学习和其他技术/数据库的所有当前和未来启动中，以更好地了解所有生物体的神经退行性疾病，尤其是对于那些希望更好地了解人类 ADRD 风险和进展的研究。
2.

将 OL 和 OPC 生物标志物添加到分子面板中，研究受各种 ADRD 影响的人群的基础、转化和临床诊断、预后和治疗研究。
3.

将 OL 和 OPC 生物标志物添加到系统生物学、ADRD 动物和细胞模型的原位和体内表征中。
4.

ADRD 资助机构应寻找并优先考虑在其科学或治疗方法中包含 OL 和/或 OPC 的项目。在比较和对比 ADRD 中涉及的细胞类型的大规模数据收集计划中，应强烈考虑纳入 OL。

不适用。

老：: 少突胶质细胞
OPC：: 少突胶质细胞祖细胞
ADRD：: 阿尔茨海默病和相关痴呆症

Auguste YSS、Ferro A、Kahng JA、Xavier AM、Dixon JR、Vrudhula U 等人。少突胶质细胞前体细胞在小鼠回路重塑过程中吞噬突触。国家神经科学。2022;25:1273–8.

论文： CAS PubMed， PubMed， Central Google Scholar
Akay LA， Effenberger AH， Tsai LH.各行各业的细胞：突触、血管和免疫功能中的少突胶质细胞前体细胞。基因开发 2021;35:180–98.

论文： CAS PubMed， PubMed， Central Google Scholar
Hirschfeld LR、Risacher SL、Nho K、Saykin AJ。阿尔茨海默病中的髓鞘修复：生物途径和潜在治疗方法综述。Transl 神经退化者。2022;11:47.

论文： CAS PubMed， PubMed， Central Google Scholar
Fields RD， Bukalo O. Myelin 留下回忆。国家神经科学。2020;23:469–70.

论文： CAS PubMed， PubMed， Central Google Scholar
菲利普斯 T，罗斯坦 JD。少突胶质细胞：神经元的代谢支持者。J Clin 投资。2017;127:3271–80.

文章： PubMed PubMed Central Google Scholar
Marangon D， Boccazzi M， Lecca D， Fumagalli M. 少突胶质细胞功能的调节：靶向脂质代谢和细胞外基质进行髓鞘修复。临床医学杂志 2020;9：470。

论文： CAS PubMed， PubMed， Central Google Scholar
Peferoen L， Kipp M， Valk P， Noort JM， Amor S. 少突胶质细胞-小胶质细胞在中枢神经系统中的串扰。免疫学。2014;141:302–13.

论文： CAS PubMed， PubMed， Central Google Scholar
Johnson ECB、Bian S、Haque RU、Carter EK、Watson CM、Gordon BA 等人。脑脊液蛋白质组学定义了常染色体显性遗传阿尔茨海默病的自然病程。国家医学 2023;29:1979–88.

论文： CAS PubMed， PubMed， Central Google Scholar
Schuster KH、Zalon AJ、Zhang H、DiFranco DM、Stec NR、Haque Z 等人。少突胶质细胞成熟受损是 SCA3 疾病发病机制的早期特征。神经科学杂志。2022;42:1604–17.

论文： CAS PubMed， PubMed， Central Google Scholar
Blanchard JW， Akay LA， Davila-Velderrain J， von Maydell D， Mathys H， Davidson SM， et al. APOE4 通过少突胶质细胞中的胆固醇失调损害髓鞘形成。自然界。2022;611:769–79.

论文： CAS PubMed， PubMed， Central Google Scholar
NF-κB 是少突胶质细胞有丝分裂后衰老和随后白质丢失的关键介质。Mol 神经退化者。2023;18:24.

论文： CAS PubMed， PubMed， Central Google Scholar
Gazestani V、Kamath T、Nadaf NM、Dougalis A、Burris SJ、Rooney B 等人。人类皮层的早期阿尔茨海默病病理涉及瞬时细胞状态。细胞。2023;186：4438–e445323。

论文： CAS PubMed， PubMed， Central Google Scholar
Sasmita AO、Depp C、Nazarenko T、Sun T、Siems SB、Ong EC 等人。少突胶质细胞产生淀粉样蛋白β，并有助于阿尔茨海默病模型小鼠与神经元一起形成斑块。国家神经科学。2024;27:1668–74.

论文： CAS PubMed， PubMed， Central Google Scholar
Parrilla GE、Gupta V、Wall RV、Salkar A、Basavarajappa D、Mirzaei M 等人。髓鞘在神经退行性变中的作用：对药物靶点和神经保护策略的影响。神经科学牧师。2024;35:271–92.

论文 CAS PubMed Google Scholar

下载参考资料

与往常一样，感谢支持 BrightFocus 基金会项目阿尔茨海默病研究的热心捐助者。

作者和单位

BrightFocus Foundation， 22512 Gateway Center Drive，克拉克斯堡，马里兰州， 20871，美国
Sharyn L. Rossi & Diane E. Bovenkamp

作者

莎琳·罗西查看作者出版物

您也可以在 PubMed Google Scholar 中搜索此作者
黛安·博文坎普查看作者出版物

您也可以在 PubMed Google Scholar 中搜索此作者

贡献

SLR 构思了这项工作，并在 DEB 的贡献下编写了初稿。

通讯作者

与 Sharyn L. Rossi 的通信。

利益争夺

SLR 和 DEB 没有与此观点相关的财务或非财务竞争利益。

道德认可

不适用。

同意

不适用。

出版商注

施普林格·自然（Springer Nature）对已发布的地图和机构隶属关系中的管辖权主张保持中立。

开放获取本文根据 Creative Commons Attribution 4.0 International License 获得许可，该许可允许以任何媒体或格式使用、共享、改编、分发和复制，前提是您对原作者和来源给予适当的信任，提供指向 Creative Commons 许可的链接，并说明是否进行了更改。本文中的图像或其他第三方材料包含在文章的知识共享许可中，除非在材料的致谢行中另有说明。如果材料未包含在文章的 Creative Commons 许可中，并且您的预期用途未被法律法规允许或超出允许的用途，您将需要直接从版权所有者处获得许可。要查看此许可证的副本，请访问 http://creativecommons.org/licenses/by/4.0/。知识共享公共领域专用弃权（http://creativecommons.org/publicdomain/zero/1.0/）适用于本文中提供的数据，除非在数据的鸣谢行中另有说明。

重印本和权限