Oligodendroglial Cells in Alzheimer’s Disease

Butt, Arthur M.; Chacon-De-La-Rocha, Irene; Rivera, Andrea

doi:10.1007/978-981-13-9913-8_12

Cited by 73 publications

(65 citation statements)

References 59 publications

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“…However, murine models of β‐amyloid deposition show reparative responses at later stages of the disease [15,114‐116]. No similar increase in Olig2 and NG2‐immunoreactive cells occurs in AD, as shown in the present work and in previous studies [15‐106,109,110]. However, a certain normalization of the mRNA expression of several myelin‐related genes here observed in AD without co‐morbidities has its counterpart in transgenic models.…”

Section: Discussionsupporting

confidence: 76%

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White matter alterations in Alzheimer’s disease without concomitant pathologies

Ferrer

Andrés‐Benito

2020

Neuropathology Appl Neurobio

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Aims Most individuals with AD neuropathological changes have co‐morbidities which have an impact on the integrity of the WM. This study analyses oligodendrocyte and myelin markers in the frontal WM in a series of AD cases without clinical or pathological co‐morbidities. Methods From a consecutive autopsy series, 206 cases had neuropathological changes of AD; among them, only 33 were AD without co‐morbidities. WM alterations were first evaluated in coronal sections of the frontal lobe in every case. Then, RT‐qPCR and immunohistochemistry were carried out in the frontal WM of AD cases without co‐morbidities to analyse the expression of selected oligodendrocyte and myelin markers. Results WM demyelination was more marked in AD with co‐morbidities when compared with AD cases without co‐morbidities. Regarding the later, mRNA expression levels of MBP, PLP1, CNP, MAG, MAL, MOG and MOBP were preserved at stages I–II/0–A when compared with middle‐aged (MA) individuals, but significantly decreased at stages III–IV/0–C. This was accompanied by reduced expression of NG2 and PDGFRA mRNA, reduced numbers of NG2‐, Olig2‐ and HDAC2‐immunoreactive cells and reduced glucose transporter immunoreactivity. Partial recovery of some of these markers occurred at stages V–VI/B–C. Conclusions The present observations demonstrate that co‐morbidities have an impact on WM integrity in the elderly and in AD, and that early alterations in oligodendrocytes and transcription of genes linked to myelin proteins in WM occur in AD cases without co‐morbidities. These are followed by partial recovery attempts at advanced stages. These observations suggest that oligodendrocytopathy is part of AD.

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Section: Discussionsupporting

confidence: 76%

“…Reduced numbers of oligodendrocytes and altered control of glucose and lactate metabolites necessary for trophic support for axons may produce, in turn, altered axonal function, and axonal degeneration. This scenario takes place at a limited rate in the ageing human brain [19], but its potentially damaging effect is overwhelmed in AD [110].…”

Section: Discussionmentioning

confidence: 99%

White matter alterations in Alzheimer’s disease without concomitant pathologies

Ferrer

Andrés‐Benito

2020

Neuropathology Appl Neurobio

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“…In SOD1 mice, a mouse model of ALS, astrocytic NF-κB promotes degeneration of motor neurons and accelerates disease progression [138]. Subtle white matter changes are found in neurodegenerative diseases as early as pre-clinical AD where the NF-κB pathway could play a role in exacerbating inflammatory signaling [139]. Intervention in this pathway is effective, as demonstrated by the MS drug laquinimod, which inhibits astrocytic NF-κB expression [4,134].…”

Section: Astrocytes In Neuroinflammationmentioning

confidence: 99%

Astrocyte and Oligodendrocyte Cross-Talk in the Central Nervous System

Nutma

Gent

Amor

et al. 2020

Cells

120

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Over the last decade knowledge of the role of astrocytes in central nervous system (CNS) neuroinflammatory diseases has changed dramatically. Rather than playing a merely passive role in response to damage it is clear that astrocytes actively maintain CNS homeostasis by influencing pH, ion and water balance, the plasticity of neurotransmitters and synapses, cerebral blood flow, and are important immune cells. During disease astrocytes become reactive and hypertrophic, a response that was long considered to be pathogenic. However, recent studies reveal that astrocytes also have a strong tissue regenerative role. Whilst most astrocyte research focuses on modulating neuronal function and synaptic transmission little is known about the cross-talk between astrocytes and oligodendrocytes, the myelinating cells of the CNS. This communication occurs via direct cell-cell contact as well as via secreted cytokines, chemokines, exosomes, and signalling molecules. Additionally, this cross-talk is important for glial development, triggering disease onset and progression, as well as stimulating regeneration and repair. Its critical role in homeostasis is most evident when this communication fails. Here, we review emerging evidence of astrocyte-oligodendrocyte communication in health and disease. Understanding the pathways involved in this cross-talk will reveal important insights into the pathogenesis and treatment of CNS diseases.

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“…Myelination is essential for the high speed transmission in the neural network; myelinated fibers have at minimum 10-fold faster conduct velocity than unmyelinated fibers with the same diameter [232]. Loss in myelination impairs performance of CNS, leads to neurodegeneration, and is among the earliest abnormalities during AD pathogenesis (see review [233]). Oligodendrocytes are vulnerable to oxidative DNA damage, which contributes to loss of neurons and onset of AD (see review [228]).…”

Section: Discussionmentioning

confidence: 99%

Contributions of DNA Damage to Alzheimer’s Disease

Lin

Kapoor

et al. 2020

IJMS

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Alzheimer's disease (AD) is the most common type of neurodegenerative disease. Its typical pathology consists of extracellular amyloid-β (Aβ) plaques and intracellular tau neurofibrillary tangles. Mutations in the APP, PSEN1, and PSEN2 genes increase Aβ production and aggregation, and thus cause early onset or familial AD. Even with this strong genetic evidence, recent studies support AD to result from complex etiological alterations. Among them, aging is the strongest risk factor for the vast majority of AD cases: Sporadic late onset AD (LOAD). Accumulation of DNA damage is a well-established aging factor. In this regard, a large amount of evidence reveals DNA damage as a critical pathological cause of AD. Clinically, DNA damage is accumulated in brains of AD patients. Genetically, defects in DNA damage repair resulted from mutations in the BRAC1 and other DNA damage repair genes occur in AD brain and facilitate the pathogenesis. Abnormalities in DNA damage repair can be used as diagnostic biomarkers for AD. In this review, we discuss the association, the causative potential, and the biomarker values of DNA damage in AD pathogenesis.Int. J. Mol. Sci. 2020, 21, 1666 2 of 26 amyloid (senile) plaques in AD brain [9][10][11]. Furthermore, CDK5 activities affect DNA damage response [12], supporting a linkage of DNA damage with AD [13,14].Aβ peptides are directly produced by sequential cleavages of APP by βand γ-secretase; the proteolytic c-terminal fragment of APP (CTFβ) of β-secretase is cleaved within the cell membrane by γ-secretase to generate neurotoxic Aβ peptides with length ranging from 38-43 residues [15][16][17][18][19]. The 40 residue Aβ peptide (Aβ 1-40 ) is the major product, accounting for more than 50% of Aβ peptides [9,17]. Although the Aβ 1-42 peptide consists of less than 10% of Aβ peptides [16,17], it is more neurotoxic and associates with a higher risk of AD because of its propensity of aggregation [9]. The importance of Aβ in AD pathogenesis is illustrated by mutations of APP, PSEN1, and PREN2 genes in familial AD with the latter two encoding the presenilin 1 and presenilin 2 subunit of γ-secretase. Individuals with these mutations develop early onset dementia in an autosomal-dominant manner [20]; the typical onset starts between 30 and 50 years of age in PSEN1 mutant carriers with some being affected at in their 20s [20,21]. γ-secretase with mutant presenilin 1 or presenilin 2 subunit favors Aβ 1-42 production [16,17]. These genetic observations led to formation of the amyloid cascade hypothesis, in which abnormal Aβ drives AD pathogenesis via regulating other pathological events including tau pathology [22][23][24][25][26][27]. This hypothesis is supported by the similar pathological features between familial AD and sporadic late onset AD (LOAD) [20]. Although familial AD constitutes less than 1% of AD cases [28,29], the hypothesis has been widely accepted to guide research in advancing the understanding of both familial AD and LOAD in the past two decades [30,31].Nonetheless, it is becoming in...

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Oligodendroglial Cells in Alzheimer’s Disease

Cited by 73 publications

References 59 publications

White matter alterations in Alzheimer’s disease without concomitant pathologies

White matter alterations in Alzheimer’s disease without concomitant pathologies

Astrocyte and Oligodendrocyte Cross-Talk in the Central Nervous System

Contributions of DNA Damage to Alzheimer’s Disease

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