ArticleCell death and differentiation2020
Impaired adult neurogenesis is an early event in Alzheimer's disease neurodegeneration, mediated by intracellular Aβ oligomers.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 88 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.
- Early Signs of Molecular Defects in iPSC-Derived Neural Stems Cells from Patients with Familial Parkinson's Disease.Biomolecules · 2022Pooled it
- Pathophysiological roles of neural stem cells in neuropsychiatric diseases: from plasticity to pharmacological targeting.Acta pharmacologica Sinica · 2026Review
- Folic Acid Metabolism and Its Impact on Neurogenesis: Molecular Mechanisms and Therapeutic Potential.Molecular neurobiology · 2026Review
- DNA Methylation Landscape of ReNcell Common Neural Progenitor Cell Lines Reveals Distinct Lineage Bias.Biology · 2026Article
- Notum1a Inhibition promotes neurogenesis in the adult zebrafish brain.Scientific reports · 2025Article
- Hematopoietic EphA4 deficiency alters microglial heterogeneity and improves chronic spatial memory after brain injury.Scientific reports · 2025Article
- TREM2 Alleviates Neuroinflammation and Improves Neurogenesis in ApoEMolecular neurobiology · 2025Article
- Intervention Role of APOE in CNS Diseases: APOE Actions and APOE Neurogenesis Capability.Molecular neurobiology · 2025Review
- Melatonin Supplementation in Alzheimer's disease: The Potential Role in Neurogenesis.Molecular neurobiology · 2025Review
- Boosting Neurogenesis as a Strategy in Treating Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Enhanced differentiation of neural progenitor cells in Alzheimer's disease into vulnerable immature neurons.iScience · 2025Article
- The subventricular zone structure, function and implications for neurological disease.Genes & diseases · 2025Review
- Carbon ion stimulation therapy reverses iron deposits and microglia driven neuroinflammation and induces cognitive improvement in an Alzheimer's disease mouse model.Scientific reports · 2025Article
- Review
- Inhibition of repulsive guidance molecule A ameliorates diabetes-induced cognitive decline and hippocampal neurogenesis impairment in mice.Communications biology · 2025Article
- Quantification and correlation of amyloid-β plaque load, glial activation, GABAergic interneuron numbers, and cognitive decline in the young TgF344-AD rat model of Alzheimer's disease.Frontiers in aging neuroscience · 2025Article
- The active metabolite of Epimedii Folium promotes hippocampal neurogenesis in APP/PS1 mice by alleviating mitochondrial dysfunction.Frontiers in pharmacology · 2025Article
- CRISPR/Cas9-Based therapeutics as a promising strategy for management of Alzheimer's disease: progress and prospects.Frontiers in cellular neuroscience · 2025Review
- Article
- Melatonin Augments the Expression of Core Transcription Factors in Aged and Alzheimer's Patient Skin Fibroblasts.Biology · 2024Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alterations of adult neurogenesis have been reported in several Alzheimer's disease (AD) animal models and human brains, while defects in this process at presymptomatic/early stages of AD have not been explored yet. To address this, we investigated potential neurogenesis defects in Tg2576 transgenic mice at 1.5 months of age, a prodromal asymptomatic age in terms of Aβ accumulation and neurodegeneration. We observe that Tg2576 resident and SVZ-derived adult neural stem cells (aNSCs) proliferate significantly less. Further, they fail to terminally differentiate into mature neurons due to pathological, tau-mediated, and microtubule hyperstabilization. Olfactory bulb neurogenesis is also strongly reduced, confirming the neurogenic defect in vivo. We find that this phenotype depends on the formation and accumulation of intracellular A-beta oligomers (AβOs) in aNSCs. Indeed, impaired neurogenesis of Tg2576 progenitors is remarkably rescued both in vitro and in vivo by the expression of a conformation-specific anti-AβOs intrabody (scFvA13-KDEL), which selectively interferes with the intracellular generation of AβOs in the endoplasmic reticulum (ER). Altogether, our results demonstrate that SVZ neurogenesis is impaired already at a presymptomatic stage of AD and is caused by endogenously generated intracellular AβOs in the ER of aNSCs. From a translational point of view, impaired SVZ neurogenesis may represent a novel biomarker for AD early diagnosis, in association to other biomarkers. Further, this study validates intracellular Aβ oligomers as a promising therapeutic target and prospects anti-AβOs scFvA13-KDEL intrabody as an effective tool for AD treatment.
Indexed as
Identifiers
What OpenQuestion holds
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.