Decreased Oligodendrocyte Nuclear Diameter in Alzheimer's Disease and Lewy Body Dementia

Gagyi, Eva; Kormos, Bernadett; Castellanos, Karla J.; Valyi‐Nagy, Klara; Korneff, Dennis; LoPresti, Patrizia; Woltjer, Randy; Vályi-Nagy, Tibor

doi:10.1111/j.1750-3639.2012.00595.x

Cited by 31 publications

(22 citation statements)

References 35 publications

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“…The authors reported that myelinating oligodendrocytes are highly sensitive to oxidative stress due to their higher metabolic demand, higher iron, and lipid content. Reduction of the diameter of oligodendrocyte nuclei in AD patients in parahippocampal white matter was also reported [ 35 ] while the mean nuclear diameter of neurons remained unchanged. Alzheimer’s-related changes in oligodendrocytes for human studies and animal models are summarized in Table 1 .…”

Section: Introductionmentioning

confidence: 56%

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

Nasrabady

Rizvi

Goldman

et al. 2018

acta neuropathol commun

508

388

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Alzheimer’s disease (AD) is conceptualized as a progressive consequence of two hallmark pathological changes in grey matter: extracellular amyloid plaques and neurofibrillary tangles. However, over the past several years, neuroimaging studies have implicated micro- and macrostructural abnormalities in white matter in the risk and progression of AD, suggesting that in addition to the neuronal pathology characteristic of the disease, white matter degeneration and demyelination may be also important pathophysiological features. Here we review the evidence for white matter abnormalities in AD with a focus on myelin and oligodendrocytes, the only source of myelination in the central nervous system, and discuss the relationship between white matter changes and the hallmarks of Alzheimer’s disease. We review several mechanisms such as ischemia, oxidative stress, excitotoxicity, iron overload, Aβ toxicity and tauopathy, which could affect oligodendrocytes. We conclude that white matter abnormalities, and in particular myelin and oligodendrocytes, could be mechanistically important in AD pathology and could be potential treatment targets.

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Section: Introductionmentioning

confidence: 56%

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

Nasrabady

Rizvi

Goldman

et al. 2018

acta neuropathol commun

508

388

View full text Add to dashboard Cite

show abstract

“…When dealing with human tissues, many variables must be taken into account that could potentially influence study results including age, PMI, sex, and other factors. The post-mortem integrity of post-translational protein modifications is largely unknown; however, in an AD patient population, factors such as age, gender, and PMI, had no significant effect on neuronal nuclear diameter 55 . Additionally, rapid autopsy programs are not well established 56 57 .…”

Section: Discussionmentioning

confidence: 91%

Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer’s disease

Kim

Franck

Kang

et al. 2015

Sci Rep

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Alzheimer’s disease (AD) is the most common form of dementia; however, mechanisms and biomarkers remain unclear. Here, we examined hippocampal CA4 and dentate gyrus subfields, which are less studied in the context of AD pathology, in post-mortem AD and control tissue to identify possible biomarkers. We performed mass spectrometry-based proteomic analysis combined with label-free quantification for identification of differentially expressed proteins. We identified 4,328 proteins, of which 113 showed more than 2-fold higher or lower expression in AD hippocampi than in control tissues. Five proteins were identified as putative AD biomarkers (MDH2, PCLO, TRRAP, YWHAZ, and MUC19 isoform 5) and were cross-validated by immunoblotting, selected reaction monitoring, and MALDI imaging. We also used a bioinformatics approach to examine upstream signalling interactions of the 113 regulated proteins. Five upstream signalling (IGF1, BDNF, ZAP70, MYC, and cyclosporin A) factors showed novel interactions in AD hippocampi. Taken together, these results demonstrate a novel platform that may provide new strategies for the early detection of AD and thus its diagnosis.

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“…White matter involvement in PD is limited, whereas white matter involvement in DLB is variable, mainly affecting the posterior lobes, and often linked with associated Alzheimer's disease (AD) pathology (Bohnen and Albin, 2011;Nedelska et al, 2015;Firbank et al, 2016;Joki et al, 2018). Decreased size of oligodendroglial nuclei has been described in LBD independently of the concomitant AD pathology (Gagyi et al, 2012). The reasons and functional consequences are not known.…”

Section: Lewy Body Diseasesmentioning

confidence: 99%

Oligodendrogliopathy in neurodegenerative diseases with abnormal protein aggregates: The forgotten partner

Ferrer

2018

Progress in Neurobiology

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Oligodendrocytes are in contact with neurons, wrap axons with a myelin sheath that protects their structural integrity, and facilitate nerve conduction. Oligodendrocytes also form a syncytium with astrocytes which interacts with neurons, promoting reciprocal survival mediated by activity and by molecules involved in energy metabolism and trophism. Therefore, oligodendrocytes are key elements in the normal functioning of the central nervous system. Oligodendrocytes are affected following different insults to the central nervous system including ischemia, traumatism, and inflammation. The term oligodendrogliopathy highlights the prominent role of altered oligodendrocytes in the pathogenesis of certain neurological diseases, not only in demyelinating diseases and most leukodystrophies, but also in aging and age-related neurodegenerative diseases with abnormal protein aggregates. Most of these diseases are characterized by the presence of abnormal protein deposits, forming characteristic and specific inclusions in neurons and astrocytes but also in oligodendrocytes, thus signaling their involvement in the disease. Emerging evidence suggests that such deposits in oligodendrocytes are not mere bystanders but rather are associated with functional alterations. Moreover, operative modifications in oligodendrocytes are also detected in the absence of oligodendroglial inclusions in certain diseases. The present review focuses first on general aspects of oligodendrocytes and precursors, and their development and functions, and then introduces and updates alterations and dysfunction of oligodendrocytes in selected neurodegenerative diseases with abnormal protein aggregates such as multiple system atrophy, Lewy body diseases, tauopathies, Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal lobar degeneration with TDP-43 inclusions (TDP-43 proteinopathies), and Creutzfeldt-Jakob´s disease as a prototypical human prionopathy.

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Decreased Oligodendrocyte Nuclear Diameter in Alzheimer's Disease and Lewy Body Dementia

Cited by 31 publications

References 35 publications

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

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

Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer’s disease

Oligodendrogliopathy in neurodegenerative diseases with abnormal protein aggregates: The forgotten partner

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