White matter changes in Alzheimer’s disease: a focus on myelin and oligodendrocytes

Nasrabady, Sara Ebrahimi; Rizvi, Batool; Goldman, James E.; Brickman, Adam M.

doi:10.1186/s40478-018-0515-3

Cited by 510 publications

(436 citation statements)

References 89 publications

(114 reference statements)

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“…The myelin sheath maintains the action potentials and ion currents in the axons, thus reducing energy consumption and increasing conduction velocity, whereby a myelinated axon is more efficient at transducing a signal than an unmyelinated one (124). The disruption of oligodendrocyte function has been implicated in a number of disorders, including AD, PD, multiple sclerosis, and cerebral palsy (reviewed elsewhere (125)(126)(127)(128)]. Any event that targets oligodendrocytes will invariably result in demyelination.…”

Section: Oligodendrocytesmentioning

confidence: 99%

“…A number of studies have observed a loss of oligodendrocyte lineage cells in the gray matter associated with amyloid plaques (133,134). Changes in myelin damage and oligodendrocytes in the white matter have also been observed and have been reviewed in detail by Nasrabady et al (125). These alterations may be caused by oxidative stress, apoptosis, or neuroinflammation or a combination thereof (124,125).…”

Section: Oligodendrocytesmentioning

confidence: 99%

“…Changes in myelin damage and oligodendrocytes in the white matter have also been observed and have been reviewed in detail by Nasrabady et al (125). These alterations may be caused by oxidative stress, apoptosis, or neuroinflammation or a combination thereof (124,125). As yet, the mechanisms involved in oligodendrocyte dysfunction in AD have not been deciphered and remain a potential clinical target.…”

Section: Oligodendrocytesmentioning

confidence: 99%

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Unravelling the glial response in the pathogenesis of Alzheimer's disease

2018

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Alzheimer's disease is a progressive, incurable neurodegenerative disease targeting specific neuronal populations within the brain while neighboring neurons appear unaffected. The focus for defining mechanisms has therefore been on the pathogenesis in affected neuronal populations and developing intervention strategies to prevent their cell death. However, there is growing recognition of the importance of glial cells in the development of pathology. Determining exactly how glial cells are involved in the disease process and the susceptibility of the aging brain provides unprecedented challenges. The present review examines recent studies attempting to unravel the glial response during the course of disease and how this action may dictate the outcome of neurodegeneration. The importance of regional heterogeneity of glial cells within the CNS during healthy aging and disease is examined to understand how the glial cells may contribute to neuronal susceptibility or resilience during the neurodegenerative process.—Alibhai, J. D., Diack, A. B., Manson, J. C. Unravelling the glial response in the pathogenesis of Alzheimer's disease. 32, 5766–5777 (2018). http://www.fasebj.org

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Section: Oligodendrocytesmentioning

confidence: 99%

Section: Oligodendrocytesmentioning

confidence: 99%

Section: Oligodendrocytesmentioning

confidence: 99%

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Unravelling the glial response in the pathogenesis of Alzheimer's disease

2018

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“…During past decades, a great number of studies have focused on addressing whether the abnormally increased brain iron is an initial cause for the development of neurodegeneration and neuronal death. A number of excellent reviews on the updated understanding of this question have recently been published …”

Section: Brain Iron Misregulation Is a Common Pathway In Neurodegenermentioning

confidence: 99%

Hepcidin and its therapeutic potential in neurodegenerative disorders

Qian

2019

Medicinal Research Reviews

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Abnormally high brain iron, resulting from the disrupted expression or function of proteins involved in iron metabolism in the brain, is an initial cause of neuronal death in neuroferritinopathy and aceruloplasminemia, and also plays a causative role in at least some of the other neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Friedreich's ataxia. As such, iron is believed to be a novel target for pharmacological intervention in these disorders. Reducing iron toward normal levels or hampering the increases in iron associated with age in the brain is a promising therapeutic strategy for all iron‐related neurodegenerative disorders. Hepcidin is a crucial regulator of iron homeostasis in the brain. Recent studies have suggested that upregulating brain hepcidin levels can significantly reduce brain iron content through the regulation of iron transport protein expression in the blood‐brain barrier and in neurons and astrocytes. In this review, we focus on the discussion of the therapeutic potential of hepcidin in iron‐associated neurodegenerative diseases and also provide a systematic overview of recent research progress on how misregulated brain iron metabolism is involved in the development of multiple neurodegenerative disorders.

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“…8 Changes in functional connectivity are also widespread, 9 as well as oscillatory changes. 10 White matter (WM) changes can also be seen in PD, although less reliably than other neurodegenerative diseases, such as Alzheimer's disease 11 and Huntington's disease. 12 Alterations of the WM microstructure can differentiate PD subjects from healthy controls as well as other PD subtypes, and correlate with some PD symptoms.…”

mentioning

confidence: 99%

White matter myelin profiles linked to clinical subtypes of Parkinson's disease

Baumeister

Kim

Zhu

et al. 2018

Magnetic Resonance Imaging

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Background White matter (WM) microstructural integrity is important for effective brain functioning and alterations have been shown in many neurodegenerative diseases. Purpose To investigate WM myelin profiles and their relation to clinical features of Parkinson's disease (PD). Study Type Retrospective cross‐sectional. Population In all, 29 PD subjects and 15 healthy controls. Field Strength/Sequence Multiecho GRASE with 10 msec echo spacing and echo planar imaging (EPI) diffusion‐weighted (b‐value = 700 with 32 gradient directions) on a 3T scanner. Assessment Myelin water fraction (MWF) and fractional anisotropy (FA) across 20 WM regions of interest (ROIs) were compared between groups. Partial least squares (PLS) was used to associate MWF and FA with clinical and behavioral measures. Statistical Tests Group comparisons were done using two‐sample t‐tests. PLS was assessed with permutation tests. Bootstrapping was used to investigate the robustness of imaging features. Results No group differences in myelin content could be detected with univariate tests. A three‐component PLS model linked MWF profiles to clinical phenotypes but no FA profiles. The three components appeared to follow along broad motor/nonmotor subtypes of “akinetic‐rigid,” “tremor‐predominant,” and “depression/apathy” subtypes, respectively. The first component showed associations between overall motor scores (r = –0.43, P = 0.0196) and cognitive performance (r = 0.44, P = 0.0171) with interhemispheric and long‐range association fibers. A second component linked overall motor scores (r = –0.58, P = 0.0009) and tremor scores (r = –0.48, P = 0.0091) to predominantly projection fibers. The last component related depression (r = –0.60, P = 0.0006) and apathy scores (r = –0.66, P = 0.0001 and r = –49, P = 0.0072) to a mixture of association and projection fibers. Data Conclusion MWF was robustly linked to distinct clinical subtypes of PD and may serve as an additional tool to characterize the disease. Level of Evidence: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:164–174.

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White matter changes in Alzheimer’s disease: a focus on myelin and oligodendrocytes

Cited by 510 publications

References 89 publications

Unravelling the glial response in the pathogenesis of Alzheimer's disease

Unravelling the glial response in the pathogenesis of Alzheimer's disease

Hepcidin and its therapeutic potential in neurodegenerative disorders

White matter myelin profiles linked to clinical subtypes of Parkinson's disease

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