Spreading of Alzheimer’s disease inflammatory signaling through soluble micro-RNA

Lukiw, Walter J.; Alexandrov, Peter N.; Zhao, Yuhai; Hill, James M.; Bhattacharjee, Surjyadipta

doi:10.1097/wnr.0b013e32835542b0

Cited by 82 publications

(94 citation statements)

References 24 publications

(85 reference statements)

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“…After miRNAs were first found in CSF [28], several more studies have demonstrated the presence of miRNAs in CSF and their potentials as biomarkers for neurological disease [32][33][34][35]. Further, a study comparing miRNA expression profile from serum and CSF has revealed that miRNA expression pattern is quite consistent among different subjects when miRNAs are from the same type of bio-fluid (serum or CSF).…”

Section: Journal Of Pharmacogenomics and Pharmacoproteomicsmentioning

confidence: 99%

MicroRNAs Role in the Central Nervous System Development and Abnormalities

Liu¹,

Wang²

2016

J Pharmacogenomics Pharmacoproteomics

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Section: Journal Of Pharmacogenomics and Pharmacoproteomicsmentioning

confidence: 99%

MicroRNAs Role in the Central Nervous System Development and Abnormalities

Liu¹,

Wang²

2016

J Pharmacogenomics Pharmacoproteomics

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“…Age-matched control and 5xFAD brain and/or retina at 0, 1.5, 3 and 5 months were analyzed for Aβ40 and Aβ42 peptide and COX-2 and CRP protein levels using ELISA and Western analysis [3,[5][6][7][8]. Further details on the quality control for these 5xFAD brain and retinal samples, sample handling and analysis have been recently published [3,[18][19][20][21].…”

Section: Reagents Brain and Retinal Tissues Protein Extraction And mentioning

confidence: 99%

“…Out of multiple Tg-AD models studied by our laboratory (Tg2576, PSAPP, 3xTg-AD, etc.,) the 5xFAD model exhibits the most rapid and prolific accumulation of Aβ42 peptides in the brain and retina of any Tg-AD animal studied to date [2][3][4]. Whether amyloidogenesis originates independently in the brain and retina, or whether amyloidogenic signals originate in the brain and spread via the primary visual cortex and thalamus to the retina is open to question, but current data now favor the latter possibility [4][5][6][7][8]. Several laboratories have independently studied the effects of supplementing the diets of amyloidoverexpressing Tg-AD murine models (Tg-2576, APP/PS1, 5xFAD, etc.,) with aluminum (as chloride, lactate, maltolate or sulfate) and have evaluated the impact of ingested aluminum with pathological outcome [9][10][11][12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

P3‐117: Progressive Inflammatory Pathology in the Retina of Aluminum‐Fed 5XFAD Transgenic Mice

Pogue¹,

Lukiw

Percy

et al. 2016

Alzheimer's & Dementia

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At least 57 murine transgenic models for Alzheimer's disease (Tg-AD) have been developed to overexpress the 42 amino acid amyloid-beta (Aβ42) peptide in the central nervous system (CNS). These 'humanized murine Tg-AD models' have greatly expanded our understanding of the contribution of Aβ42 peptide-mediated pro-inflammatory neuropathology to the AD process. A number of independent laboratories using different amyloid-overexpressing Tg-AD models have shown that supplementation of murine Tg-AD diets and/or drinking water with aluminum significantly enhances Aβ42 peptide-mediated inflammatory pathology and AD-type cognitive change compared to animals receiving control diets. In humans AD-type pathology appears to originate in the limbic system and progressively spreads into primary processing and sensory regions such as the retina. In these studies, for the first time, we assess the propagation of Aβ42 and inflammatory signals into the retina of 5xFAD Tg-AD amyloid-overexpressing mice whose diets were supplemented with aluminum. The two most interesting findings were (1) that similar to other Tg-AD models, there was a significantly accelerated development of Aβ42 and inflammatory pathology in 5xFAD Tg-AD mice fed aluminum; and (2) in aluminumsupplemented animals, markers for inflammatory pathology appeared in both the brain and the retina as evidenced by an evolving presence of Aβ42 peptides, and accompanied by inflammatory markers -cyclooxygenase-2 (COX-2) and C-reactive protein (CRP). The results indicate that in the 5xFAD Tg-AD model aluminum not only enhances an Aβ42-mediated inflammatory degeneration of the brain but also appears to induce AD-type pathology in an anatomically-linked primary sensory area that involves vision.

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“…Given that some human cancer cells secrete miRNAs into their extracellular environment and body fl uids, [24][25][26] it was hypothesized that MB cell lines may secrete miRNAs into their spent culture medium. To test this hypothesis, 3 cell lines representing MB subtypes D341 and D283 (metastasis-related group 3 and group 4 MB subtypes) [27] and DAOY (sonic hedgehog-related) were cultured individually for 72 h in vitro and miRNAs expression was analyzed in the lysates of each MB cell line and in their corresponding culture media.…”

Section: Detection Of Ex-mirnas In Cultured Medium Of Mb Cell Lines Bmentioning

confidence: 99%

Detection and quantification of extracellular microRNAs in medulloblastoma

Shalaby¹,

Fiaschetti²,

Baulande³

et al. 2015

J Cancer Metastasis Treat

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Aim: Medu lloblastoma (MB) is the most common malignant brain tumor in children. The crucial role of extracellular-microRNAs (ex-miRNAs) in cancer has been widely recognized; however, their role in MB remains unknown. This study aimed to investigate MB-driven ex-miRNAs. Methods: Microarray analysis was used to disclose the identity and quantity of key miRNAs excreted in culture-medium (CM) of 3 human MB cell lines and cere brospinal fl uid (CSF) of brain tumors (including MB) and leukemia patients. MiRNA expression was validated by quantitative reverse transcription polymerase chain reaction. Results: We have demonstrated that the 3 MB cell lines tested commonly expressed 1,083 miRNAs in their spent CM. Among them, 57 miRNAs were specifi c to the CM of metastasis-related cell lines which represents the aggressive group 3 and group 4 MB subtypes. A signifi cant number (1,254) of ex-miRNAs were identifi ed in the CSF of a MB patient. Eighty-six of these miRNAs were found to be differentially expressed in this patient's CSF compared with controls. Interestingly, 3 metastasis-associated miRNAs over-represented in CM of metastasis-related MB cell lines were found to be signifi cantly enriched in the CSF of the MB patient. Conclusion: Although more samples are required to fully verify these results, our work provides the fi rst evidence for the presence of a signifi cant amount of miRNAs excreted extracellularly by MB cells and raises the possibility that, in the near future, miRNAs could be probed in CSF of MB patients and serve as novel biological markers.

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Spreading of Alzheimer’s disease inflammatory signaling through soluble micro-RNA

Cited by 82 publications

References 24 publications

MicroRNAs Role in the Central Nervous System Development and Abnormalities

MicroRNAs Role in the Central Nervous System Development and Abnormalities

P3‐117: Progressive Inflammatory Pathology in the Retina of Aluminum‐Fed 5XFAD Transgenic Mice

Detection and quantification of extracellular microRNAs in medulloblastoma

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