The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index; 20 of the 48 sources its claims cite were checked for support.
microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain
Open accessAbstract
Dysregulation of amyloid-β (Aβ) metabolism is critical for Alzheimer's disease (AD) pathogenesis. Mounting evidence suggests that apolipoprotein E (ApoE) is involved in Aβ metabolism. ATP-binding cassette transporter A1 (ABCA1) is a key regulator of ApoE lipidation, which affects Aβ levels. Therefore, identifying regulatory mechanisms of ABCA1 expression in the brain may provide new therapeutic targets for AD. Here, we demonstrate that microRNA-33 (miR-33) regulates ABCA1 and Aβ levels in the brain. Overexpression of miR-33 impaired cellular cholesterol efflux and dramatically increased extracellular Aβ levels by promoting Aβ secretion and impairing Aβ clearance in neural cells. In contrast, genetic deletion of mir-33 in mice dramatically increased ABCA1 levels and ApoE lipidation, but it decreased endogenous Aβ levels in cortex. Most importantly, pharmacological inhibition of miR-33 via antisense oligonucleotide specifically in the brain markedly decreased Aβ levels in cortex of APP/PS1 mice, representing a potential therapeutic strategy for AD. SIGNIFICANCE STATEMENT Brain lipid metabolism, in particular Apolipoprotein E (ApoE) lipidation, is critical to Aβ metabolism and Alzheimer's disease (AD). Brain lipid metabolism is largely separated from the periphery due to blood–brain barrier and different repertoire of lipoproteins. Therefore, identifying the novel regulatory mechanism of brain lipid metabolism may provide a new therapeutic strategy for AD. Although there have been studies on brain lipid metabolism, its regulation, in particular by microRNAs, is relatively unknown. Here, we demonstrate that inhibition of microRNA-33 increases lipidation of brain ApoE and reduces Aβ levels by inducing ABCA1. We provide a unique approach for AD therapeutics to increase ApoE lipidation and reduce Aβ levels via pharmacological inhibition of microRNA in vivo.
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Written from the paper’s full text.
TL;DR
miR-33 is enriched in the brain, directly suppresses ABCA1, and regulates ApoE lipidation and Aβ metabolism in neural cells. Genetic deletion or brain-specific antisense inhibition of miR-33 increases ABCA1/ApoE lipidation and lowers cortical Aβ in mice, suggesting a potential AD therapeutic strategy.
Key findings
- miR-33 is highly enriched in brain and expressed in neurons, astrocytes, and microglia, with relatively higher expression in neurons.
- miR-33 directly targets the ABCA1 3′UTR; overexpression suppressed ABCA1 in N2a cells and primary astrocytes, while mir-33 deletion increased cortical ABCA1.
- miR-33 overexpression impaired ApoE-mediated cholesterol efflux, increased CTFβ and secreted Aβ, and impaired Aβ clearance/degradation; miR-33-resistant Abca1 ORF rescued these effects.
- mir-33 deletion increased ApoE lipidation and decreased endogenous cortical Aβ40 by 33% and Aβ42 by 40%; brain-specific anti-miR-33 in APP/PS1 mice significantly decreased Aβ40 (p = 0.0286) and showed a trend for Aβ42 (p = 0.0954, 24% difference between means).
Methods
- In vitro studies used mouse N2a, human H4-APPsw neuroglioma cells, and mouse primary astrocytes, with luciferase reporter assays, cholesterol efflux assays, Aβ secretion/clearance/degradation assays, qRT-PCR, and Western blotting.
- In vivo studies used mir-33 knockout mice and 2-month-old APP/PS1 transgenic mice treated with 30 µg/d anti-miR-33 or mismatch control for 4 weeks via intracerebroventricular infusion using osmotic pumps; female mice were used.
- Cortical Aβ was measured by sandwich ELISA and normalized to total protein; ApoE lipidation was assessed by native PAGE/Western blot; statistical testing used two-tailed Student’s t test after variance/normality checks, with two-way ANOVA for degradation assays.
Limitations
- The paper states that no human clinical trial has demonstrated that an antisense oligonucleotide can reduce a target RNA or protein in the brain, and that blood-brain barrier delivery remains a major obstacle for clinical application.
- The paper notes that miRNA overexpression may produce artificial effects by surpassing biological buffering capacity, making endogenous modulation important; the study addresses this with knockout and brain-specific inhibition.
- Evident from the text: most mechanistic work is in cell lines and mice, with no behavioral/cognitive outcomes reported; anti-miR-33 reduced Aβ42 only as a trend; and all in vivo experiments used female mice, with small sample sizes.
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Claims the paper makes
52 Own result · 14 Own interpretation · 9 Partly supported · 6 Own method · 5 Supported · 4 No full text of the sources · 4 Not checked yet · 3 Supported so far · 3 Sources not found · 1 No basis given · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“and lipidation status have been shown to strongly influence A metabolism (Kim et al., 2009a,b;Bien-Ly et al., 2012).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Brain lipid metabolism, in particular Apolipoprotein E (ApoE) lipidation, is critical to A metabolism and Alzheimer's disease (AD).
What the sources say
- Not matchedcites Kim et al., 2009a,b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites Bien-Ly et al., 2012 sourceExperimental — accuracy not yet measured
The Results section, “Halving the levels of apoE significantly attenuates Aβ accumulation in aged mice” (page unavailable), reports that reducing apoE3 or apoE4 levels reduced Aβ accumulation in aged mice. The copy does not establish that apoE lipidation status influences Aβ metabolism; its Discussion mentions other lipid-metabolism processes only as a possible explanation requiring further study. (LLM, conf=0.88)
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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- Not matched
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Mounting evidence has demonstrated that dysregulation of cholesterol metabolism is implicated in AD pathogenesis (Kim et al., 2009a;Di Paolo and Kim, 2011).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Brain lipid metabolism, in particular Apolipoprotein E (ApoE) lipidation, is critical to A metabolism and Alzheimer's disease (AD).
What the sources say
- Not matchedcites Kim et al., 2009a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Supportedcites Di Paolo and Kim, 2011 source
The Abstract states that cholesterol has been linked to AD pathogenesis and that epidemiological studies support a role for cholesterol in it. The section on cholesterol metabolism and transport in amyloidogenesis further describes how altered cholesterol balance and efflux affect Aβ pathology, supporting the paraphrase. (LLM, conf=0.93)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In addition to its role in A secretion, ABCA1 has been also shown to decrease A levels by promoting extracellular A clearance in both neurons and glial cells (Jiang et al., 2008;Kim et al., 2012).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > miR-33 regulates A secretion and A clearance in neural cells
What the sources say
- Not checked — no full text of the sourcecites Jiang et al., 2008 source
- Partly supportedcites Kim et al., 2012 sourceExperimental — accuracy not yet measured
The Results section ('Impairment of Aβ clearance by miR-106b is rescued by ABCA1 ORF expression'; page unavailable) reports that restoring ABCA1 rescued impaired extracellular Aβ clearance in neuronal cells. The Discussion says ABCA1 overexpression did not increase clearance above baseline in those cells and only suggests a possible clearance mechanism in microglia. The claim therefore overstates the evidence for promoted clearance in both neurons and glial cells. (LLM, conf=0.89)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“We and others previously demonstrated that ABCA1 decreases A secretion by inhibiting BACE1-mediated APP cleavage without affecting BACE1 expression in neuronal cells (Sun et al., 2003;Kim et al., 2012).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > miR-33 regulates A secretion and A clearance in neural cells
What the sources say
- Not checked — no full text of the sourcecites Sun et al., 2003 source
- Supportedcites Kim et al., 2012 source
The Results section, “Alteration in APP processing by miR-106b is rescued by ABCA1 ORF expression” (page unavailable), reports that ABCA1 expression decreased secreted Aβ and CTFβ without altering BACE1 protein levels. The paper identifies CTFβ as a product of β-secretase cleavage of APP, supporting the paraphrase about reduced BACE1-mediated cleavage in neuronal cells. (LLM, conf=0.88)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Furthermore, several lines of in vitro evidence support the critical role of ABCA1 in A production, although how ABCA1 regulates A production remains to be clarified (Koldamova et al., 2003;Sun et al., 2003;Kim et al., 2007).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Brain lipid metabolism, in particular Apolipoprotein E (ApoE) lipidation, is critical to A metabolism and Alzheimer's disease (AD).
What the sources say
- Partly supportedcites Koldamova et al., 2003 sourceExperimental — accuracy not yet measured
The Abstract (page unavailable) reports decreased Aβ production in cultured cells after LXR/RXR ligand treatment, with or without ABCA1-mediated cholesterol depletion. The Discussion (page unavailable) says ABCA1 may affect APP processing and Aβ secretion, but also says the ligand effects might depend on factors beyond ABCA1. This supports a possible role, not the stronger claim that this study establishes a critical role for ABCA1. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites Sun et al., 2003 source
- Supportedcites Kim et al., 2007 source
In the results section on Aβ peptide generation (page not supplied), the paper reports that ABCA1 expression reduced Aβ generation by 55% in cultured CHO-APP cells. Its conclusion describes ABCA1 as playing a significant role in suppressing Aβ-generating APP processing, supporting the cited claim about in vitro evidence. (LLM, conf=0.93)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“ApoE lipidation by ABCA1 is critical for A clearance (Jiang et al., 2008;Kim et al., 2012).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
What the sources say
- Not checked — no full text of the sourcecites Jiang et al., 2008 source
- Partly supportedcites Kim et al., 2012 sourceExperimental — accuracy not yet measured
The Discussion reports that fully lipidated apoE is required for effective Aβ degradation in microglia and that reducing ABCA1 impaired extracellular Aβ clearance. But it says ABCA1 *may* affect clearance by facilitating apoE lipidation and that the mechanism remains unclear; it does not establish that this route is critical. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the paper
“intrathecal ASO injection to nonhuman primates led to accumulation of ASO in the cortical neuronal and glial cells (Rigo et al., 2014).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
What the sources say
- Supportedcites Rigo et al., 2014 source
The nonhuman-primate pharmacokinetics passage (page not provided) reports cortical accumulation after intrathecal bolus injection. The accompanying immunohistochemistry passage reports ASO accumulation in gray-matter cell bodies consistent with neuronal and glial cell targeting. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“we and others have shown that ABCA1 is required for the effective clearance of A by neuronal and glial cells”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
What the sources say
- Not checked — no full text of the sourcecites Jiang et al., 2008 source
- Partly supportedcites Kim et al., 2012 sourceExperimental — accuracy not yet measured
The Results section ('Impairment of Aβ clearance by miR-106b is rescued by ABCA1 ORF expression'; page not provided) shows that restoring ABCA1 rescued impaired Aβ clearance in neuronal cells, but only when the medium contained FBS. The Discussion (page not provided) describes ABCA1's possible role in microglial clearance as a suggestion, not an established requirement. The claim therefore extends the neuronal-cell finding to glial cells and omits the experimental condition. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“mir-33 gene deletion markedly increased ABCA1 levels (Fig. 7 A, B) and decreased endogenous A 40 levels by 33% and A 42 levels by 40% in cortex (Fig. 7C,D).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Inhibition of miR-33 effectively decreases A levels in the brain
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that mir-33 deletion significantly facilitated extracellular A degradation, compared with WT (Fig. 6C,D).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > miR-33 regulates A secretion and A clearance in neural cells
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 20
- It may state two separate claims as one. 16
- The quote only partly states this claim. 2
Every source the paper cites for this claim was checked and supports it.
In the paper
“Several genetic association studies have suggested possible association between polymorphisms in ABCA1 and AD risk (Koldamova et al., 2010).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Brain lipid metabolism, in particular Apolipoprotein E (ApoE) lipidation, is critical to A metabolism and Alzheimer's disease (AD).
What the sources say
- Supportedcites Koldamova et al., 2010 source
Section 3.1 reports at least 12 studies of ABCA1 variants and AD risk, including studies that found significant associations. It also describes conflicting results and says no integrated hypothesis has emerged, consistent with the citing sentence’s cautious wording. (LLM, conf=0.93)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“ATP-binding cassette transporter A1 (ABCA1) is a major cholesterol transporter that transfers cellular cholesterol onto lipid-poor apolipoproteins and regulates ApoE lipidation in the brain (Koldamova et al., 2014).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Brain lipid metabolism, in particular Apolipoprotein E (ApoE) lipidation, is critical to A metabolism and Alzheimer's disease (AD).
What the sources say
- Supportedcites Koldamova et al., 2014 source
The cholesterol-efflux section states that ABCA1 transfers cellular cholesterol to lipid-free apolipoproteins. The CNS section identifies apoE as the main brain acceptor of lipids translocated by ABCA1 and reports that loss of functional ABCA1 affects apoE lipidation in the brain. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“several in vitro studies have suggested that ABCA1 inhibits A secretion in neuronal cells by modulating APP proteolysis and membrane lipid homeostasis (Di Paolo and Kim, 2011).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
What the sources say
- Partly supportedcites Di Paolo and Kim, 2011 sourceExperimental — accuracy not yet measured
In ‘Role of cholesterol metabolism and transport in amyloidogenesis’ (page not provided), the review reports that increased ABCA1 lowers Aβ levels in cultured cells and that ABCA1 promotes cholesterol efflux. Its discussion of lipid-dependent APP processing is broader; it does not establish that ABCA1 lowers Aβ secretion specifically in neuronal cells by modulating APP proteolysis. (LLM, conf=0.84)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Pharmacological inhibition of miR-33 increased plasma high-density lipoprotein cholesterol levels in mice (Horie et al., 2010;Najafi-Shoushtari et al., 2010;Rayner et al., 2011a) and primates (Rayner et al., 2011b;Rottiers et al., 2013), leading to a marked reduction of atherosclerosis phenotypes.”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Brain lipid metabolism, in particular Apolipoprotein E (ApoE) lipidation, is critical to A metabolism and Alzheimer's disease (AD).
What the sources say
- Not checked — no full text of the sourcecites Horie et al., 2010 source
- Partly supportedcites Najafi-Shoushtari et al., 2010 sourceExperimental — accuracy not yet measured
The Results report that antisense inhibition of miR-33 significantly increased plasma HDL cholesterol in mice. This paper does not report miR-33 inhibition in primates or demonstrate a reduction in atherosclerosis phenotypes; the citing sentence assigns the primate finding to other citations. (LLM, conf=0.88)
- Not matchedcites Rayner et al., 2011a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Somewhat unexpectedly, the vast majority of miRNA knock-out mice examined thus far lack any strong phenotypes under normal physiological conditions (Ebert and Sharp, 2012;Mendell and Olson, 2012).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
What the sources say
- Partly supportedcites Ebert and Sharp, 2012 sourceExperimental — accuracy not yet measured
The “Absent and variable phenotypes” section says several mouse miRNA knockouts show no gross phenotype and gives miR-208 as an example with little phenotype under normal conditions. It does not establish that the vast majority of mouse knockouts examined lack strong phenotypes; its “most” statement concerns worms, not mice. No page number is available in our copy. (LLM, conf=0.86)
- Partly supportedcites Mendell and Olson, 2012 sourceExperimental — accuracy not yet measured
In “Lessons from miRNA loss-of-function studies in model organisms” (page unavailable), the review says the majority of approximately 25 mouse miRNA knockouts examined lacked embryonic developmental defects, and many showed abnormalities only under stress. This supports the general point, but it does not establish that the vast majority lacked any strong phenotype under normal physiological conditions; its explicit mouse finding is narrower and says “majority.” (LLM, conf=0.82)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“there have been several successful cases that have identified small-molecule modulators of miRNAs (Velagapudi et al., 2015)”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
What the sources say
- Supportedcites Velagapudi et al., 2015 source
The review describes multiple successful examples, including small molecules that inhibit maturation of miR-21, miR-372, miR-373, and miR-96 (Introduction, “Targeting RNA biogenesis by inhibiting Dicer and Drosha processing”; page unavailable). Its Outlook & Future Directions section also concludes that the examples show miRNA expression can be altered with small molecules. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“there have been substantial advances in the small RNA delivery technology into the brain.”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
What the sources say
- Not checked — no full text of the sourcecites Kumar et al., 2007 source
- Supportedcites Pulford et al., 2010 source
The Introduction describes a transvascular method for delivering siRNA across the blood-brain barrier, and the Discussion reports that the paper's own intravenously administered complexes reached cells throughout the mouse brain. Together, these passages support the broad statement that small-RNA delivery technology for the brain had advanced; the supplied passages do not provide page numbers. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites Alvarez-Erviti et al., 2011 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Several miRNAs and antisense oligonucleotides (ASOs) are currently under investigation in clinical trials for various diseases (Kanasty et al., 2013;van Rooij and Kauppinen, 2014;Gaudet et al., 2015).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
What the sources say
- Not checked — no full text of the sourcecites Kanasty et al., 2013 source
- Supportedcites van Rooij and Kauppinen, 2014 source
Table 1 in “miRNA-based therapeutics: from bench to bedside” lists three clinical-phase miRNA-based therapies: two antimiRs for hepatitis C and a miR-34 mimic for liver cancer. The paper also identifies antimiRs as antisense oligonucleotides in “Inhibition of miRNA function.” (LLM, conf=0.87)
- Supportedcites Gaudet et al., 2015 source
Gaudet et al. provide an example of an antisense oligonucleotide being investigated in a clinical trial: the Results describe a randomized phase 2 study of ISIS 304801 in patients with hypertriglyceridemia. In this multi-citation sentence, the paper supports the ASO-trial example; it does not need to establish the separate claims about miRNAs or other diseases. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Pharmacological modulations of disease-associated miRNAs appeared to be well tolerated with promising outcomes in animal models and human patients (van Rooij and Kauppinen, 2014).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
What the sources say
- Supportedcites van Rooij and Kauppinen, 2014 source
The Concluding remarks state that pharmacological modulation of disease-associated miRNAs showed promising therapeutic potential and appeared well tolerated in short-term studies of animal disease models and human patients. The claim closely paraphrases this finding; the source limits its assessment to short-term data. (LLM, conf=0.94)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For the first time, we demonstrate here that genetic deletion and pharmacological inhibition, using antisense oligonucleotide, of miR-33 decreased A levels in the brain.”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“miR-33 was expressed in all neural cell types with relatively higher expression in neurons, compared with glial cells (Fig. 1C).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > miR-33 is highly enriched in the brain
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similar results were observed in human H4 neuroglioma cells expressing APPsw transfected with miR-33 (Fig. 4C,D).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > miR-33 regulates A secretion and A clearance in neural cells
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“deletion of miR-33 increased ApoE lipidation and facilitated extracellular A degradation, leading to significant reduction of brain A levels, compared with WT.”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“overexpression of miR-33 impaired ApoE lipidation and decreased A clearance by neuronal and glial cells.”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Compared with WT mice (n ϭ 8), ABCA1 levels were dramatically increased in cortex of mir-33 knock-out mice (n ϭ 7) at 4 months of age, without altering APP levels (A, B).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the anti-miR-33 treatment group (n ϭ 9), A 40 levels were significantly decreased ( p ϭ 0.0286) (C) and A 42 levels showed a trend toward decrease ( p ϭ 0.0954) (D), compared with the mismatch control (n ϭ 6).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“ApoE is a major cholesterol carrier in the brain (Kim et al., 2009a).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Brain lipid metabolism, in particular Apolipoprotein E (ApoE) lipidation, is critical to A metabolism and Alzheimer's disease (AD).
What the sources say
- Not matchedcites Kim et al., 2009a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Apolipoprotein E (APOE) genotype is the strongest genetic risk factor for AD, with the 4 allele acting as an AD risk factor, whereas the 2 allele is protective (Kim et al., 2009a).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Introduction
What the sources say
- Not matchedcites Kim et al., 2009a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
In the paper
“Previous studies have suggested that the main effect of APOE isoforms on AD risk is via their effect on A metabolism (Kim et al., 2009a).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Introduction
What the sources say
- Not matchedcites Kim et al., 2009a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Dysregulation of A peptide metabolism is hypothesized to initiate pathogenic cascades that lead to Alzheimer's disease (AD) (Haass and Selkoe, 2007).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Introduction
What the sources say
- Not checked — no full text of the sourcecites Haass and Selkoe, 2007 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, our data suggest that miR-33 regulates extracellular A levels by modulating A secretion as well as A degradation.”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > miR-33 regulates A secretion and A clearance in neural cells
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Experiments were repeated 3 times.”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Cholesterol efflux assay.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“miRNAs often show strong cell typeand tissue-specific regulation of their targets (Landgraf et al., 2007;Jovic ˇic ´et al., 2013).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
What the sources say
- Not checked — no full text of the sourcecites Landgraf et al., 2007 source
- Not matchedcites Jovic ˇic ´et al., 2013
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“After confirmation that the data did not violate the assumptions of parametric testing, the data were analyzed with a two-tailed Student's t test (Graph-Pad Prism 5).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Statistical analysis.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the presence of miR-33 resistant Abca1 without 3ЈUTR (Abca1 ORF), miR-33 did not affect ABCA1 levels nor A levels in N2a cells expressing APPsw, suggesting that miR-33 regulates A secretion via modulating ABCA1, rather than other genes (Fig. 4E,F).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > miR-33 regulates A secretion and A clearance in neural cells
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All experiments were performed in duplicate or triplicate and repeated independently 3 times.”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Animals and anti-miR-33 treatment.
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one. The quote only partly states this claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Each transfection condition was performed in triplicate, and the experiments were repeated twice.”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Animals and anti-miR-33 treatment.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Collectively, these data suggest that miR-33 regulates ApoE lipidation as well as extracellular ApoE levels in the brain.”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Deletion of mir-33 gene increases ApoE lipidation in the brain
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, ABCA1 regulation by miR-33 in the periphery does not necessarily mean that miR-33 will regulate ABCA1 in the brain.”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Previously, we demonstrated that ABCA1 expression is regulated by miR-33 in the periphery (Horie et al., 2010;Rayner et al., 2010Rayner et al., , 2011a,b),b).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Brain lipid metabolism, in particular Apolipoprotein E (ApoE) lipidation, is critical to A metabolism and Alzheimer's disease (AD).
What the sources say
- Not checked — no full text of the sourcecites Horie et al., 2010 source
- Not matchedcites Rayner et al., 2010, 2011a,b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“miR-33 is selectively deleted in cortex of miR-33 (Ϫ/Ϫ) mice without altering the expression of its host gene, SREBF2, in cortex.”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Recently, intrathecal ASO injection to human was successfully completed in the Phase I and II clinical trials (Faravelli et al., 2015).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
What the sources say
- Not checked — no full text of the sourcecites Faravelli et al., 2015 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Both trials demonstrated that intrathecal ASO injection is safe and effective.”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
What the sources say
- Not checked — no full text of the sourcecites Faravelli et al., 2015 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
The physiological function of miR-33 in the CNS and whether miR-33 has any pathological role in AD have never been investigated.
“However, the physiological function of miR-33 in the CNS and whether miR-33 has any pathological role in AD have never been investigated.”
The paper relies on this without support.
The regulation of brain lipid metabolism, in particular by microRNAs, is relatively unknown.
“Although there have been studies on brain lipid metabolism, its regulation, in particular by microRNAs, is relatively unknown.”
The paper relies on this without support.
Whether pharmacological inhibition of a miRNA can be a practical strategy to regulate brain Aβ levels in vivo has not yet been demonstrated.
“Although several in vitro studies have implicated miRNAs in AD pathogenesis, whether pharmacological inhibition of a miRNA can be a practical strategy to regulate brain A levels in vivo has not yet been demonstrated.”
The paper relies on this without support.
Brain lipid metabolism is largely separated from the periphery due to the blood-brain barrier and different repertoire of lipoproteins.
“Brain lipid metabolism is largely separated from the periphery due to blood-brain barrier and different repertoire of lipoproteins.”
The paper relies on this without support.
Our understanding of how endogenous Aβ levels are regulated is still limited.
“Despite the critical role of A metabolism in AD pathogenesis, our understanding of how endogenous A levels are regulated is still limited.”
The paper relies on this without support.
miRNA overexpression over a certain physiological level may lead to an artificial effect by surpassing biological buffering capacity of the cells.
“miRNA overexpression over a certain physiological level may lead to an artificial effect by surpassing biological buffering capacity of the cells.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“miR-33 increased extracellular Aβ levels in mouse and human neuronal cells.”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [127]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“ABCA1 is redundantly targeted by miR-106b, miR-758, and miR-33 in the brain.”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [127]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Previously, it was shown that miR‐33 negatively regulates ABCA1 in both the periphery and the brain. 15 , 16 , 17 , 18”
From Deletion of miR-33, a regulator of the ABCA1–APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice (2024) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, we demonstrated that deletion of the mir‐33 gene increases the lipidation of apoE in the brains of wild‐type mice. 17”
From Deletion of miR-33, a regulator of the ABCA1–APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice (2024) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“Previously, miR‐33 was shown to negatively regulate ABCA1 protein levels. 17 , 18”
From Deletion of miR-33, a regulator of the ABCA1–APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice (2024) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“Both genetic and pharmacologic inhibition of miR-33 decreased cortical Aβ levels. [127].”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [127]
The cited source says what the claim attributes to it.
In the citing paper
“pharmacological inhibition of miR-33 significantly increased ABCA1 level [127, 128].”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [127]
The cited source says what the claim attributes to it.
In the citing paper
“overexpression of miR-33 decreased ABCA1 levels and impaired cholesterol efflux in neuronal and glial cells [127].”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [127]
The cited source says what the claim attributes to it.
In the citing paper
“pharmacological and genetic inhibition of miR-33 significantly increased ABCA1 level and decreased amyloid β levels in the brain [16].”
From Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease (2017) · cites this paper as [16]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > A degradation assay.
“At 48 h after transfection, the cells were incubated in fresh serum-free media.After 24 h incubation, conditioned media were collected”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
“At 48 h after transfection, conditioned media were collected and were incubated with 200 nM of synthetic A 40 .”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Statistical analysis.
“the data were analyzed with a two-tailed Student's t test (Graph-Pad Prism 5).”
§ Neurobiology of Disease microRNA-33 Regulates ApoE Lipidation and Amyloid- Metabolism in the Brain > Discussion
“***p Ͻ 0.001 (two-way ANOVA).”
Citations
Cites
Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes
Alvarez-Erviti, L., Seow, Y., Yin, H., Betts, C., Lakhal, S., & Wood, M. J. A. (2011) · Nature Biotechnology · doi:10.1038/nbt.1807 · Cited by 4,930 · cited 1×
“For example, conjugation with neurotrophic virus peptide and exosome- or liposome-based nanoparticles are promising avenues of future research (Kumar et al., 2007; Pulford et al., 2010; Alvarez-Erviti et al., 2011; Roshan et al., 2014).”
BackgroundSoluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744 · cited 1×
“Dysregulation of A peptide metabolism is hypothesized to initiate pathogenic cascades that lead to Alzheimer’s disease (AD) (Haass and Selkoe, 2007).”
BackgroundA Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing
Landgraf, P., Rusu, M., Sheridan, R., Sewer, A., Iovino, N., Aravin, A., Pfeffer, S., Rice, A., Kamphorst, A. O., Landthaler, M., et al. (2007) · Cell · doi:10.1016/j.cell.2007.04.040 · Cited by 3,626
Delivery materials for siRNA therapeutics
Kanasty, R., Dorkin, J. R., Vegas, A., & Anderson, D. (2013) · Nature Materials · doi:10.1038/nmat3765 · Cited by 1,800 · cited 1×
“Several miRNAs and antisense oligonucleotides (ASOs) are currently under investigation in clinical trials for various diseases (Kanasty et al., 2013; van Rooij and Kauppinen, 2014; Gaudet et al., 2015).”
BackgroundMicroRNAs in Stress Signaling and Human Disease
Mendell, J. T., & Olson, E. N. (2012) · Cell · doi:10.1016/j.cell.2012.02.005 · Cited by 1,673 · cited 2×
“In many cases, miRNA knock-out mice showed no gross phenotype under normal physiological conditions, possibly due to the functional redundancy of multiple miRNAs for the same target gene (Ebert and Sharp, 2012; Mendell and Olson, 2012).”
BackgroundThe role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661
Self-citationJankowsky, J. L., Fadale, D. J., Anderson, J., Xu, G. M., Gonzales, V., Jenkins, N. A., Copeland, N. G., Lee, M. K., Younkin, L. H., Wagner, S. L., et al. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh019 · Cited by 1,575 · cited 2×
“Twomonth-old APPsw/PSEN1 9 (APP/PS1) transgenic mice overexpressing Swedish mutant APP695 and human PSEN1 with an exon 9 deletion (Jankowsky et al., 2004) were treated with 30 g/d of anti-miR-33 or mismatch control for 4 weeks via intracerebroventricular infusion using an osmotic pump (Alzet)…”
MethodRoles for MicroRNAs in Conferring Robustness to Biological Processes
Ebert, M. S., & Sharp, P. A. (2012) · Cell · doi:10.1016/j.cell.2012.04.005 · Cited by 1,564 · cited 2×
“In many cases, miRNA knock-out mice showed no gross phenotype under normal physiological conditions, possibly due to the functional redundancy of multiple miRNAs for the same target gene (Ebert and Sharp, 2012; Mendell and Olson, 2012).”
BackgroundMiR-33 Contributes to the Regulation of Cholesterol Homeostasis
Rayner, K. J., Suárez, Y., Dávalos, A., Parathath, S., Fitzgerald, M. L., Tamehiro, N., Fisher, E. A., Moore, K. J., & Fernández-Hernando, C. (2010) · Science · doi:10.1126/science.1189862 · Cited by 1,260 · cited 1×
“Previously, we demonstrated that ABCA1 expression is regulated by miR-33 in the periphery (Horie et al., 2010; Rayner et al., 2010, 2011a,b).”
BackgroundTransvascular delivery of small interfering RNA to the central nervous system
Kumar, P., Wu, H., McBride, J. L., Jung, K.-E., Hee Kim, M., Davidson, B. L., Kyung Lee, S., Shankar, P., & Manjunath, N. (2007) · Nature · doi:10.1038/nature05901 · Cited by 1,246 · cited 1×
“For example, conjugation with neurotrophic virus peptide and exosome- or liposome-based nanoparticles are promising avenues of future research (Kumar et al., 2007; Pulford et al., 2010; Alvarez-Erviti et al., 2011; Roshan et al., 2014).”
BackgroundLinking lipids to Alzheimer's disease: cholesterol and beyond
Di Paolo, G., & Kim, T.-W. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3012 · Cited by 972
MicroRNA-33 and the SREBP Host Genes Cooperate to Control Cholesterol Homeostasis
Najafi-Shoushtari, S. H., Kristo, F., Li, Y., Shioda, T., Cohen, D. E., Gerszten, R. E., & Näär, A. M. (2010) · Science · doi:10.1126/science.1189123 · Cited by 957 · cited 2×
“Pharmacological inhibition of miR-33 increased plasma high-density lipoprotein cholesterol levels in mice (Horie et al., 2010; Najafi-Shoushtari et al., 2010; Rayner et al., 2011a) and primates (Rayner et al.”
BackgroundApoE Promotes the Proteolytic Degradation of Aβ
Jiang, Q., Lee, C. Y. D., Mandrekar, S., Wilkinson, B., Cramer, P., Zelcer, N., Mann, K., Lamb, B., Willson, T. M., Collins, J. L., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.04.010 · Cited by 876 · cited 3×
“In addition to its role in A secretion, ABCA1 has been also shown to decrease A levels by promoting extracellular A clearance in both neurons and glial cells (Jiang et al., 2008; Kim et al., 2012).”
BackgroundSelf-citationInhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides
Rayner, K. J., Esau, C. C., Hussain, F. N., McDaniel, A. L., Marshall, S. M., van Gils, J. M., Ray, T. D., Sheedy, F. J., Goedeke, L., Liu, X., et al. (2011) · Nature · doi:10.1038/nature10486 · Cited by 706 · cited 3×
“Previously, we demonstrated that ABCA1 expression is regulated by miR-33 in the periphery (Horie et al., 2010; Rayner et al., 2010, 2011a,b).”
BackgroundMethodSelf-citationRayner, K. J., Sheedy, F. J., Esau, C. C., Hussain, F. N., Temel, R. E., Parathath, S., van Gils, J. M., Rayner, A. J., Chang, A. N., Suarez, Y., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57275 · Cited by 690 · cited 3×
“Previously, we demonstrated that ABCA1 expression is regulated by miR-33 in the periphery (Horie et al., 2010; Rayner et al., 2010, 2011a,b).”
BackgroundMethodSelf-citationDevelopment of microRNA therapeutics is coming of age
van Rooij, E., & Kauppinen, S. (2014) · EMBO Molecular Medicine · doi:10.15252/emmm.201100899 · Cited by 625 · cited 2×
“Several miRNAs and antisense oligonucleotides (ASOs) are currently under investigation in clinical trials for various diseases (Kanasty et al., 2013; van Rooij and Kauppinen, 2014; Gaudet et al., 2015).”
BackgroundAntisense Inhibition of Apolipoprotein C-III in Patients with Hypertriglyceridemia
Gaudet, D., Alexander, V. J., Baker, B. F., Brisson, D., Tremblay, K., Singleton, W., Geary, R. S., Hughes, S. G., Viney, N. J., Graham, M. J., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1400283 · Cited by 528
Wahrle, S. E., Jiang, H., Parsadanian, M., Legleiter, J., Han, X., Fryer, J. D., Kowalewski, T., & Holtzman, D. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407963200 · Cited by 474 · cited 1×
“Moreover, animal studies have demonstrated that ABCA1 levels regulate A deposition in vivo (HirschReinshagen et al., 2004; Wahrle et al., 2004, 2005, 2008; Koldamova et al., 2005).”
BackgroundSelf-citationMicroRNA regulation of Alzheimer's Amyloid precursor protein expression
Hébert, S. S., Horré, K., Nicolaï, L., Bergmans, B., Papadopoulou, A. S., Delacourte, A., & De Strooper, B. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.11.009 · Cited by 436 · cited 2×
“Recently, microRNAs (miRNAs) have emerged as a new class of therapeutic targets for various diseases, including neurodegenerative disorders (Nelson and Keller, 2007; Hébert et al., 2009).”
BackgroundDeficiency of ABCA1 Impairs Apolipoprotein E Metabolism in Brain
Hirsch-Reinshagen, V., Zhou, S., Burgess, B. L., Bernier, L., McIsaac, S. A., Chan, J. Y., Tansley, G. H., Cohn, J. S., Hayden, M. R., & Wellington, C. L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407962200 · Cited by 385
Horie, T., Ono, K., Horiguchi, M., Nishi, H., Nakamura, T., Nagao, K., Kinoshita, M., Kuwabara, Y., Marusawa, H., Iwanaga, Y., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008499107 · Cited by 384 · cited 6×
“We previously reported the generation of the mir-33 knock-out mice (Horie et al., 2010).”
BackgroundInfluentialSelf-citationOverexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease
Wahrle, S. E., Jiang, H., Parsadanian, M., Kim, J., Li, A., Knoten, A., Jain, S., Hirsch-Reinshagen, V., Wellington, C. L., Bales, K. R., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33622 · Cited by 370 · cited 2×
“Moreover, animal studies have demonstrated that ABCA1 levels regulate A deposition in vivo (HirschReinshagen et al., 2004; Wahrle et al., 2004, 2005, 2008; Koldamova et al., 2005).”
BackgroundResultSelf-citationLack of ABCA1 Considerably Decreases Brain ApoE Level and Increases Amyloid Deposition in APP23 Mice
Koldamova, R., Staufenbiel, M., & Lefterov, I. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504513200 · Cited by 350 · cited 1×
“Moreover, animal studies have demonstrated that ABCA1 levels regulate A deposition in vivo (HirschReinshagen et al., 2004; Wahrle et al., 2004, 2005, 2008; Koldamova et al., 2005).”
BackgroundDeletion of Abca1 Increases Aβ Deposition in the PDAPP Transgenic Mouse Model of Alzheimer Disease
Wahrle, S. E., Jiang, H., Parsadanian, M., Hartman, R. E., Bales, K. R., Paul, S. M., & Holtzman, D. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508780200 · Cited by 325 · cited 1×
“Moreover, animal studies have demonstrated that ABCA1 levels regulate A deposition in vivo (HirschReinshagen et al., 2004; Wahrle et al., 2004, 2005, 2008; Koldamova et al., 2005).”
BackgroundSelf-citationRigo, F., Chun, S. J., Norris, D. A., Hung, G., Lee, S., Matson, J., Fey, R. A., Gaus, H., Hua, Y., Grundy, J. S., et al. (2014) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.212407 · Cited by 283
Kim, J., Castellano, J. M., Jiang, H., Basak, J. M., Parsadanian, M., Pham, V., Mason, S. M., Paul, S. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.11.013 · Cited by 274 · cited 8×
“Mounting evidence has demonstrated that dysregulation of cholesterol metabolism is implicated in AD pathogenesis (Kim et al., 2009a; Di Paolo and Kim, 2011).”
BackgroundMethodInfluentialSelf-citationJovičić, A., Roshan, R., Moisoi, N., Pradervand, S., Moser, R., Pillai, B., & Luthi-Carter, R. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.0600-12.2013 · Cited by 251 · cited 8×
“Many miRNAs show unique cell-type-specific expression patterns in different neural cell types, such as neurons, astrocytes, and microglia (Jovičić et al., 2013).”
BackgroundInfluentialKoldamova, R. P., Lefterov, I. M., Ikonomovic, M. D., Skoko, J., Lefterov, P. I., Isanski, B. A., DeKosky, S. T., & Lazo, J. S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300044200 · Cited by 237 · cited 1×
“Furthermore, several lines of in vitro evidence support the critical role of ABCA1 in A production, although how ABCA1 regulates A production remains to be clarified (Koldamova et al., 2003; Sun et al., 2003; Kim et al., 2007).”
BackgroundKim, W. S., Rahmanto, A. S., Kamili, A., Rye, K.-A., Guillemin, G. J., Gelissen, I. C., Jessup, W., Hill, A. F., & Garner, B. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607831200 · Cited by 191 · cited 1×
“Furthermore, several lines of in vitro evidence support the critical role of ABCA1 in A production, although how ABCA1 regulates A production remains to be clarified (Koldamova et al., 2003; Sun et al., 2003; Kim et al., 2007).”
BackgroundExpression of Liver X Receptor Target Genes Decreases Cellular Amyloid β Peptide Secretion
Sun, Y., Yao, J., Kim, T.-W., & Tall, A. R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300760200 · Cited by 179 · cited 5×
“…ApoE levels in the brain. miR-33 regulates A secretion and A clearance in neural cells We and others previously demonstrated that ABCA1 decreases A secretion by inhibiting BACE1-mediated APP cleavage without affecting BACE1 expression in neuronal cells (Sun et al., 2003; Kim et al., 2012).”
BackgroundResultInfluentialmiR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression
Kim, J., Yoon, H., Ramírez, C. M., Lee, S.-M., Hoe, H.-S., Fernández-Hernando, C., & Kim, J. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2011.11.010 · Cited by 173 · cited 12×
“Western blots were performed as previously described (Kim et al., 2009b, 2012).”
BackgroundMethodResultInfluentialSelf-citationBien-Ly, N., Gillespie, A. K., Walker, D., Yoon, S. Y., & Huang, Y. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0033-12.2012 · Cited by 170 · cited 2×
“We provide a unique approach for AD therapeutics to increase ApoE lipidation and reduce A levels via pharmacological inhibition of microRNA in vivo. and lipidation status have been shown to strongly influence A metabolism (Kim et al., 2009a,b; Bien-Ly et al., 2012).”
BackgroundBrain-specific knockdown of miR-29 results in neuronal cell death and ataxia in mice
Roshan, R., Shridhar, S., Sarangdhar, M. A., Banik, A., Chawla, M., Garg, M., Singh, V. P., & Pillai, B. (2014) · RNA · doi:10.1261/rna.044008.113 · Cited by 149
ATP-binding cassette transporter A1: From metabolism to neurodegeneration
Koldamova, R., Fitz, N. F., & Lefterov, I. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.05.007 · Cited by 144 · cited 1×
“ATP-binding cassette transporter A1 (ABCA1) is a major cholesterol transporter that transfers cellular cholesterol onto lipid-poor apolipoproteins and regulates ApoE lipidation in the brain (Koldamova et al., 2014).”
BackgroundSpinal muscular atrophy—recent therapeutic advances for an old challenge
Faravelli, I., Nizzardo, M., Comi, G. P., & Corti, S. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.77 · Cited by 138 · cited 1×
“Recently, intrathecal ASO injection to human was successfully completed in the Phase I and II clinical trials (Faravelli et al., 2015).”
BackgroundRottiers, V., Obad, S., Petri, A., McGarrah, R., Lindholm, M. W., Black, J. C., Sinha, S., Goody, R. J., Lawrence, M. S., deLemos, A. S., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3006840 · Cited by 121 · cited 3×
“…ApoE levels in the brain. miR-33 regulates A secretion and A clearance in neural cells We and others previously demonstrated that ABCA1 decreases A secretion by inhibiting BACE1-mediated APP cleavage without affecting BACE1 expression in neuronal cells (Sun et al., 2003; Kim et al., 2012).”
BackgroundResultInfluentialBRI2 (ITM2b) Inhibits A Deposition In Vivo
Kim, J., Miller, V. M., Levites, Y., West, K. J., Zwizinski, C. W., Moore, B. D., Troendle, F. J., Bann, M., Verbeeck, C., Price, R. W., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0891-08.2008 · Cited by 113 · cited 1×
“Cortical tissues were lysed in 0.2% diethylamine/50 mM NaCl lysis buffer with EDTA-free protease inhibitor mixture (Roche) by sonication, as previously described (Kim et al., 2008).”
MethodInfluentialSelf-citationNelson, P. T., & Keller, J. N. (2007) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000240474.27791.f3 · Cited by 110 · cited 2×
“Recently, microRNAs (miRNAs) have emerged as a new class of therapeutic targets for various diseases, including neurodegenerative disorders (Nelson and Keller, 2007; Hébert et al., 2009).”
BackgroundThe role of ATP-binding cassette transporter A1 in Alzheimer's disease and neurodegeneration
Koldamova, R., Fitz, N. F., & Lefterov, I. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.02.010 · Cited by 102 · cited 1×
“Several genetic association studies have suggested possible association between polymorphisms in ABCA1 and AD risk (Koldamova et al., 2010).”
BackgroundPulford, B., Reim, N., Bell, A., Veatch, J., Forster, G., Bender, H., Meyerett, C., Hafeman, S., Michel, B., Johnson, T., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011085 · Cited by 85 · cited 1×
“For example, conjugation with neurotrophic virus peptide and exosome- or liposome-based nanoparticles are promising avenues of future research (Kumar et al., 2007; Pulford et al., 2010; Alvarez-Erviti et al., 2011; Roshan et al., 2014).”
BackgroundSmall molecule chemical probes of microRNA function
Velagapudi, S. P., Vummidi, B. R., & Disney, M. D. (2015) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2014.10.024 · Cited by 46 · cited 1×
“In addition to ASOs, there have been several successful cases that have identified small-molecule modulators of miRNAs (Velagapudi et al., 2015), further expanding the roles of miRNAs from diagnostic tools to therapeutic targets of diseases.”
Background
Cited by
Sorted by citations
Bartel, D. P. (2018) · Cell · doi:10.1016/j.cell.2018.03.006 · Cited by 3,751
“, 2010); increased ApoE lipidation and Ab degradation in the brain (Kim et al., 2015); increased obesity and liver steatosis on high-fat diet (Horie et al.”
BackgroundApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies
Raulin, A.-C., Doss, S. V., Trottier, Z. A., Ikezu, T. C., Bu, G., & Liu, C.-C. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00574-4 · Cited by 756
“Targeting of miRNA-33 via ASO results in increased ABCA1 levels, elevated apoE lipidation, and decreased Aβ levels in mouse models [233].”
BackgroundAPOE2: protective mechanism and therapeutic implications for Alzheimer’s disease
Li, Z., Shue, F., Zhao, N., Shinohara, M., & Bu, G. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00413-4 · Cited by 306
“Intracerebroventricular infusion of anti-miR-33 oligonucleotides reduces cortical Aβ40 levels in 3-month-old APP/PS1 mice [334].”
BackgroundFunctional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases
Wu, Y.-Y., & Kuo, H.-C. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-020-00636-z · Cited by 213
“The deletion of miR-33 has been linked to AD pathology in APPswe/PESN1ΔE9 mice [118].”
BackgroundNoncoding RNAs in Alzheimer's disease
Idda, M. L., Munk, R. B., Abdelmohsen, K., & Gorospe, M. (2018) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1463 · Cited by 211
“Deletion of miR-33 in mice increased the levels of ATP-binding cassette transporter (ABCA1) and APOE lipidation, while it decreased Aβ levels in the cortex (Kim et al., 2015).”
Background
Metadata
- Authors
- Kim, J., Yoon, H., Horie, T., Burchett, J. M., Restivo, J. L., Rotllan, N., Ramírez, C. M., Verghese, P. B., Ihara, M., Hoe, H.-S., Esau, C., Fernández-Hernando, C., Holtzman, D. M., Cirrito, J. R., Ono, K., & Kim, J.
- Affiliations
- Mayo Clinic (US)
- Kyoto University (JP)
- Washington University in St. Louis (US)
- Yale University (US)
- National Cerebral and Cardiovascular Center (JP)
- Georgetown University Medical Center (US)
- Regulus Therapeutics (United States) (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2015-11-04
- Volume
- 35
- Issue
- 44
- Pages
- 14717-14726
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4635126
- OpenAlex
- W2204892940
- Cited by
- 128
- References
- 41
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 13 · 2023: 10 · 2022: 11 · 2021: 22 · 2020: 14 · 2019: 11 · 2018: 13 · 2017: 10 · 2016: 11
- FWCI
- 7.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- PubMed Central (submittedVersion)
- Funders
- BrightFocus Foundation (A2012421, A2010613)
- GHR Foundation
- National Institutes of Health (5p50ag005681-36, 5p30ns069329-02, 5p50ag016574-20)
- Center for Individualized Medicine, Mayo Clinic
- Japan Society for the Promotion of Science (15H04271)
- National Institute on Aging (AG039708, AG042513, AG016574, P50‐AG005681, P50‐AG016574, R01AG042513, R01 AG013956, R03 AG039708, R37AG013956, AG13956, AG005681)
- National Heart, Lung, and Blood Institute (R01HL107953, HL107953)
- National Institute of Neurological Disorders and Stroke (P30-NS069329, NS069329)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- microRNA-33, apolipoprotein E, amyloid-beta metabolism, ABCA1, Alzheimer's disease, cholesterol efflux, brain lipid metabolism, antisense oligonucleotides, APP/PS1 mice, amyloid-beta clearance, blood-brain barrier
- MeSH terms
- Animals, Apolipoproteins E, Base Sequence, Brain, Humans, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Amyloid beta-Peptides, Mice, Knockout, MicroRNAs, Lipid Metabolism, Mice
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