Alteration of the microRNA network during the progression of Alzheimer's disease
Open accessAbstract
An overview of miRNAs altered in Alzheimer's disease (AD) was established by profiling the hippocampus of a cohort of 41 late‐onset AD (LOAD) patients and 23 controls, showing deregulation of 35 miRNAs. Profiling of miRNAs in the prefrontal cortex of a second independent cohort of 49 patients grouped by Braak stages revealed 41 deregulated miRNAs. We focused on miR‐132‐3p which is strongly altered in both brain areas. Downregulation of this miRNA occurs already at Braak stages III and IV, before loss of neuron‐specific miRNAs. Next‐generation sequencing confirmed a strong decrease of miR‐132‐3p and of three family‐related miRNAs encoded by the same miRNA cluster on chromosome 17. Deregulation of miR‐132‐3p in AD brain appears to occur mainly in neurons displaying Tau hyper‐phosphorylation. We provide evidence that miR‐132‐3p may contribute to disease progression through aberrant regulation of mRNA targets in the Tau network. The transcription factor (TF) FOXO1a appears to be a key target of miR‐132‐3p in this pathway.
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Multiple miRNAs are dysregulated in the affected regions of AD brains.
“Recent miRNA profiling studies showed that multiple miRNAs are dysregulated in the affected regions of AD brains (Lau et al. 2013, Hebert et al. 2008, Wang et al. 2011, Delay et al. 2012, Cogswell et al. 2008, Lukiw 2007).”
From miR‐186 is decreased in aged brain and suppresses <scp>BACE</scp>1 expression (2016) · cites this paper as Lau et al. 2013
miR-186 is up-regulated in the grey matter of the prefrontal cortex in AD brains.
“On the other hand, another study reported that miR-186 is up-regulated in the grey matter of the prefrontal cortex in AD brains (Lau et al. 2013).”
From miR‐186 is decreased in aged brain and suppresses <scp>BACE</scp>1 expression (2016) · cites this paper as Lau et al. 2013
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Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · cited 1× · see citing works
“We also provide evidence that several of those miRNAs are changed according to the different Braak stages that characterize the progressive severity of the disease (Braak & Braak, 1991).”
Acetylation of Tau Inhibits Its Degradation and Contributes to Tauopathy
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“In the prefrontal cortex of LOAD patients, Tau tangles are predominantly localized in layers III/IV and V neurons (Hof et al, 1990).”
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“Among those, several miRNAs regulating BACE1 expression are known to be down-regulated in the affected regions of AD brains (Hebert et al. 2008; Nelson and Wang 2010; Lau et al. 2013; Long et al. 2014).”
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- Authors
- Lau, P., Bossers, K., Janky, R., Salta, E., Frigerio, C. S., Barbash, S., Rothman, R., Sierksma, A. S. R., Thathiah, A., Greenberg, D., Papadopoulou, A. S., Achsel, T., Ayoubi, T., Soreq, H., Verhaagen, J., Swaab, D. F., Aerts, S., & De Strooper, B.
- Affiliations
- Universitair Ziekenhuis Leuven (BE)
- Netherlands Institute for Neuroscience (NL)
- KU Leuven (BE)
- Hebrew University of Jerusalem (IL)
- ORCID
- Venue
- EMBO Molecular Medicine
- Published
- 2013-09-09
- Volume
- 5
- Issue
- 10
- Pages
- 1613-1634
- ISSN
- 1757-4676 (ISSN-L)
- 1757-4684
- PMC
- PMC3799583
- OpenAlex
- W2096128947
- Cited by
- 474
- References
- 6
- Citations by year
- 2026: 14 · 2025: 24 · 2024: 30 · 2023: 27 · 2022: 43 · 2021: 50 · 2020: 47 · 2019: 40 · 2018: 44 · 2017: 43 · 2016: 40 · 2015: 34 · 2014: 33 · 2013: 5
- FWCI
- 13.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- EMBO Molecular Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion, other-oa)
- Lirias (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion, other-oa)
- Funders
- Teva Pharmaceutical Industries
- University of Pennsylvania
- Multiple Sclerosis Society
- Belgian Federal Science Policy Office
- Fonds Wetenschappelijk Onderzoek
- Top Institute Pharma (T5-207)
- Vlaamse regering
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, microRNA dysregulation, miR-132-3p, hippocampus, prefrontal cortex, Braak stages, disease progression, tau hyperphosphorylation, FOXO1, microRNA target regulation
- MeSH terms
- Alzheimer Disease, Brain, Chromosomes, Human, Pair 17, Hippocampus, Humans, Neurons, Phosphorylation, ROC Curve, Severity of Illness Index, Cohort Studies, Down-Regulation, Cluster Analysis, tau Proteins, Disease Progression, Area Under Curve, Gene Expression Profiling, MicroRNAs, High-Throughput Nucleotide Sequencing
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