Distinct microglia profile in Creutzfeldt–Jakob disease and Alzheimer's disease is independent of disease kinetics

Krbot, Katarina; Hermann, Péter; Skorić, Magdalena Krbot; Zerr, Inga; Sepulveda‐Falla, Diego; Goebel, Stefan; Matschke, Jakob; Krasemann, Susanne; Glatzel, Markus

doi:10.1111/neup.12517

Cited by 5 publications

(3 citation statements)

References 45 publications

(147 reference statements)

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“…However Carroll et al who analyzed Tmem119 and P2ry12 transcripts at multiple time points in RML inoculated mice reported no consistent and significant changes. In CJD subjects, anti-TMEM119 immunostaining was found to be downregulated relatively to that in rapidly progressing AD, and CJD cases with concomitant Aβ pathology [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Absence of Apolipoprotein E is associated with exacerbation of prion pathology and promotes microglial neurodegenerative phenotype

Pankiewicz

Lizińczyk

Franco

et al. 2021

acta neuropathol commun

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Prion diseases or prionoses are a group of rapidly progressing and invariably fatal neurodegenerative diseases. The pathogenesis of prionoses is associated with self-replication and connectomal spread of PrPSc, a disease specific conformer of the prion protein. Microglia undergo activation early in the course of prion pathogenesis and exert opposing roles in PrPSc mediated neurodegeneration. While clearance of PrPSc and apoptotic neurons have disease-limiting effect, microglia-driven neuroinflammation bears deleterious consequences to neuronal networks. Apolipoprotein (apo) E is a lipid transporting protein with pleiotropic functions, which include controlling of the phagocytic and inflammatory characteristics of activated microglia in neurodegenerative diseases. Despite the significance of microglia in prion pathogenesis, the role of apoE in prionoses has not been established. We showed here that infection of wild type mice with 22L mouse adapted scrapie strain is associated with significant increase in the total brain apoE protein and mRNA levels and also with a conspicuous cell-type shift in the apoE expression. There is reduced expression of apoE in activated astrocytes and marked upregulation of apoE expression by activated microglia. We also showed apoE ablation exaggerates PrPSc mediated neurodegeneration. Apoe−/− mice have shorter disease incubation period, increased load of spongiform lesion, pronounced neuronal loss, and exaggerated astro and microgliosis. Astrocytes of Apoe−/− mice display salient upregulation of transcriptomic markers defining A1 neurotoxic astrocytes while microglia show upregulation of transcriptomic markers characteristic for microglial neurodegenerative phenotype. There is impaired clearance of PrPSc and dying neurons by microglia in Apoe−/− mice along with increased level of proinflammatory cytokines. Our work indicates that apoE absence renders clearance of PrPSc and dying neurons by microglia inefficient, while the excess of neuronal debris promotes microglial neurodegenerative phenotype aggravating the vicious cycle of neuronal death and neuroinflammation.

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Section: Discussionmentioning

confidence: 99%

Absence of Apolipoprotein E is associated with exacerbation of prion pathology and promotes microglial neurodegenerative phenotype

Pankiewicz

Lizińczyk

Franco

et al. 2021

acta neuropathol commun

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“…Further studies have exposed significant astrocyte morphological and immunoreactive subtype alterations in the aged and AD cerebellum 171 . Moreover, rapidly progressive AD cases have exhibited a distinct microglial phenotype in the cerebellum 172 …”

Section: Cerebellum and Admentioning

confidence: 99%

Cerebellum in Alzheimer's disease and other neurodegenerative diseases: an emerging research frontier

Yang,

Liu,

Chen

et al. 2024

MedComm

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The cerebellum is crucial for both motor and nonmotor functions. Alzheimer's disease (AD), alongside other dementias such as vascular dementia (VaD), Lewy body dementia (DLB), and frontotemporal dementia (FTD), as well as other neurodegenerative diseases (NDs) like Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and spinocerebellar ataxias (SCA), are characterized by specific and non‐specific neurodegenerations in central nervous system. Previously, the cerebellum's significance in these conditions was underestimated. However, advancing research has elevated its profile as a critical node in disease pathology. We comprehensively review the existing evidence to elucidate the relationship between cerebellum and the aforementioned diseases. Our findings reveal a growing body of research unequivocally establishing a link between the cerebellum and AD, other forms of dementia, and other NDs, supported by clinical evidence, pathological and biochemical profiles, structural and functional neuroimaging data, and electrophysiological findings. By contrasting cerebellar observations with those from the cerebral cortex and hippocampus, we highlight the cerebellum's distinct role in the disease processes. Furthermore, we also explore the emerging therapeutic potential of targeting cerebellum for the treatment of these diseases. This review underscores the importance of the cerebellum in these diseases, offering new insights into the disease mechanisms and novel therapeutic strategies.

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“…Markers of microglial phenotypes in human brains are still limited; the most widely used marker to describe activated microglia, particularly in diseased brains, has been HLA-DR, or major histocompatibility complex II protein. Ionized calcium binding adaptor molecule-1 (IBA1) and CD68 are generic markers of microglia and recruited monocytes 29 . In patients with AD, Stages V-VI of Braak, degeneration of the microglia has been observed, especially in the dentate gyrus, probably due to the accumulation of toxic tau-soluble species 30 .…”

Section: Microgliamentioning

confidence: 99%

Immunology of Alzheimer’s disease

Sosa-García¹,

Hernández-Jiménez²,

Moral-Huerta³

et al. 2019

RMN

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Alzheimer's disease (AD) is a multifactorial neurodegenerative pathology. Neuroinflammation is an early event of the presymptomatic stages in AD and contributes to its progression. We review the participation of astrocytes, microglia and blood-brain barrier cells, the mechanisms of cell death and the inflammatory factors such as chemokines, interferons and Toll-like receptors involved in progression and perpetuation of AD. Some of its prognostic and therapeutic possibilities are also mentioned. Identifying the different actors involved in inflammation and the main mechanisms of damage might allow the development of preventive strategies and treatments to fight against this devastating disease.

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Distinct microglia profile in Creutzfeldt–Jakob disease and Alzheimer's disease is independent of disease kinetics

Cited by 5 publications

References 45 publications

Absence of Apolipoprotein E is associated with exacerbation of prion pathology and promotes microglial neurodegenerative phenotype

Absence of Apolipoprotein E is associated with exacerbation of prion pathology and promotes microglial neurodegenerative phenotype

Cerebellum in Alzheimer's disease and other neurodegenerative diseases: an emerging research frontier

Immunology of Alzheimer’s disease

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