ArticleStem cell reports2022
Human tau mutations in cerebral organoids induce a progressive dyshomeostasis of cholesterol.
Article in Stem cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 37 citations in OpenAlex.
- Spatial lipidomics of the human brain: systematic review of current state and future perspectives.Molecular psychiatry · 2026Pooled it
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Brain organoids in Alzheimer disease and related tauopathies: Challenges and opportunities for translational readiness.Stem cell reports · 2026Review
- A pathogenic Tau mutation drives autophagy-lysosome dysfunction that limits Tau degradation in a model of frontotemporal dementia.Nature communications · 2026Article
- Article
- Modeling Alzheimer's disease with brain organoids: mechanisms, applications, and future directions.Frontiers in cell and developmental biology · 2026Review
- The MTRNR2L gene family and age-related macular degeneration.Frontiers in immunology · 2026Review
- From seeds to symptoms: the molecular landscape of tau seeding in Alzheimer's disease.Frontiers in neuroscience · 2026Review
- Monitoring the Dynamics of Alzheimer's Disease Biomarkers and the APOE-Tau Axis via Human Cerebral Organoids with Immuno-SERS.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Modeling Sporadic Progressive Supranuclear Palsy in 3D Midbrain Organoids: Recapitulating Disease Features for In Vitro Diagnosis and Drug Discovery.Annals of neurology · 2025Article
- GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau.Nature communications · 2025Article
- Pathways underlying selective neuronal vulnerability in Alzheimer's disease: Contrasting the vulnerable locus coeruleus to the resilient substantia nigra.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health.The Journal of cell biology · 2025Review
- The interaction between dysfunction of vasculature and tauopathy in Alzheimer's disease and related dementias.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Olanzapine enhances early brain maturation through activation of the NODAL/FOXH1 axis.iScience · 2024Article
- Astrocytes in selective vulnerability to neurodegenerative disease.Trends in neurosciences · 2024Review
- Vascularized Brain Assembloids With Enhanced Cellular Complexity Provide Insights Into the Cellular Deficits of Tauopathy.Stem cells (Dayton, Ohio) · 2024Article
- Advanced Cellular Models for Rare Disease Study: Exploring Neural, Muscle and Skeletal Organoids.International journal of molecular sciences · 2024Review
- Limitations of human brain organoids to study neurodegenerative diseases: a manual to survive.Frontiers in cellular neuroscience · 2024Review
- Cross species systems biology discovers glial DDR2, STOM, and KANK2 as therapeutic targets in progressive supranuclear palsy.Nature communications · 2023Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in the MAPT gene that encodes tau lead to frontotemporal dementia (FTD) with pathology evident in both cerebral neurons and glia. Human cerebral organoids (hCOs) from individuals harboring pathogenic tau mutations can reveal the earliest downstream effects on molecular pathways within a developmental context, generating interacting neurons and glia. We found that in hCOs carrying the V337M and R406W tau mutations, the cholesterol biosynthesis pathway in astrocytes was the top upregulated gene set compared with isogenic controls by single-cell RNA sequencing (scRNA-seq). The 15 upregulated genes included HMGCR, ACAT2, STARD4, LDLR, and SREBF2. This result was confirmed in a homozygous R406W mutant cell line by immunostaining and sterol measurements. Cholesterol abundance in the brain is tightly regulated by efflux and cholesterol biosynthetic enzyme levels in astrocytes, and dysregulation can cause aberrant phosphorylation of tau. Our findings suggest that cholesterol dyshomeostasis is an early event in the etiology of neurodegeneration caused by tau mutations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.