Genome-Wide Analysis of a Wnt1-Regulated Transcriptional Network Implicates Neurodegenerative Pathways
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A systems biology approach identifies connections between Wnt1 signaling and neurodegenerative diseases.
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Variation affecting synaptic maintenance, glial support, and cellular resilience may modify disease risk and progression.
“suggesting that variation affecting synaptic maintenance, glial support, and cellular resilience may modify disease risk and progression [98].”
From Genetic drivers of progression in Alzheimer’s disease are distinct from disease risk (2026) · cites this paper as [98]
The Introduction links GRN haploinsufficiency to inherited frontotemporal dementia, and the Discussion (Regulation of PGRN expression; page unavailable) proposes that Wnt-related changes could affect neuronal survival and the course of disease. That supports the claim’s hedged point about cellular resilience, but our copy does not establish that variation affecting synaptic maintenance or glial support modifies disease risk or progression. (LLM, conf=0.82)
Experimental — accuracy not yet measuredPathways involving Wnt signalling and developmental transcriptional regulation, relevant to genes such as ZNRF3 and MN1, have been implicated in GWAS-based pathway enrichment analyses of neurodegenerative disease.
“pathways involving Wnt signalling and developmental transcriptional regulation, relevant to genes such as ZNRF3 and MN1, have been implicated in GWAS-based pathway enrichment analyses of neurodegenerative disease”
From Genetic drivers of progression in Alzheimer’s disease are distinct from disease risk (2026) · cites this paper as [98]
The Results (Pathway analysis; page unavailable) report enrichment of Wnt-regulated genes in neurodegenerative-disease pathways. But the analysis used gene-expression data from Wnt1-treated cells, not a GWAS-based pathway enrichment analysis; the cited passages also do not establish a connection to ZNRF3 or MN1. (LLM, conf=0.90)
Experimental — accuracy not yet measuredEdge relationships using mutual information or other association measures might be necessary to accurately detect modules in time-series data, which can be non-monotonic.
“edge relationships using mutual information or other association measures might be necessary to accurately detect modules in time-series data, which can be non-monotonic46–48.”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [46]
Experimental validation of predictions from these networks showed that cross-species approaches can identify consistent, high-confidence perturbations in neurodegenerative disease.
“Experimental validation of predictions from these networks showed that this cross-species approach can identify consistent, high-confidence perturbations in neurodegenerative disease46,153.”
From Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders (2015) · cites this paper as [46]
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References 140 · Cited by 56
Research works printed but not linked: 3
- [48]MacKay DJC Information Theory, Inference, and Learning Algorithms 2003 Cambridge Univ. Press Cambridge, UK/New York
- [69]Lèbre S Stochastic Process Analysis for Genomics and Dynamic Bayesian Networks Inference PhD thesis 2007 Université d’Evry-Val-d’Essonne Evry, France
- [84]Papassotiropoulos A Wollmer MA Tsolaki M Brunner F Molyva D Lütjohann D Nitsch RM Hock C A cluster of cholesterol-related genes confers susceptibility for Alzheimer’s disease J. Clin. Psychiatry 2005 66 940 947 16013913
- Authors
- Wexler, E. M., Rosen, E., Lu, D., Osborn, G. E., Martin, E., Raybould, H., & Geschwind, D. H.
- Affiliations
- University of California, Los Angeles (US)
- University of California, Davis (US)
- Corresponding author
- Wexler, Eric M.
- Venue
- Science Signaling
- Published
- 2011-10-04
- Volume
- 4
- Issue
- 193
- Pages
- ra65-ra65
- ISSN
- 1937-9145 (ISSN-L)
- 1945-0877
- PMC
- PMC3856943
- OpenAlex
- W2043326045
- Cited by
- 56
- References
- 140
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 1 · 2022: 5 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 5 · 2015: 7 · 2014: 6 · 2013: 7 · 2012: 9
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Science Signaling (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG026938)
- National Institute of Mental Health (K08 MH74362, R01MH060233, K08MH074362, R37MH060233)
- National Institute of Neurological Disorders and Stroke (T32NS048004)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- Wnt1, Wnt signaling, non-canonical Wnt pathway, canonical Wnt pathway, transcriptional regulatory networks, gene expression oscillations, human neural progenitor cells, presenilin 1, granulin, Alzheimer's disease, frontotemporal dementia, neurodegeneration, cell death, reciprocal gene regulation
- MeSH terms
- Progranulins, Alzheimer Disease, Cells, Cultured, Gene Expression Regulation, Humans, Nerve Tissue Proteins, Transcription, Genetic, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Intercellular Signaling Peptides and Proteins, Wnt1 Protein, Presenilin-1, Genome-Wide Association Study, Frontotemporal Dementia, Wnt Signaling Pathway
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