ArticleMolecular neurodegeneration2020
Aging-relevant human basal forebrain cholinergic neurons as a cell model for Alzheimer's disease.
Article in Molecular neurodegeneration, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Direct Conversion of Fibroblast into Neurons for Alzheimer's Disease Research: A Systematic Review.Journal of Alzheimer's disease : JAD · 2023Pooled it
- Three-dimensional direct neuronal reprogramming for modeling Alzheimer's disease neuropathology.Nature protocols · 2026Review
- Subtype-specific neurons from patient iPSCs display distinct neuropathological features of Alzheimer's disease.Cell regeneration (London, England) · 2024Article
- Alcohol and stress exposure across the lifespan are key risk factors for Alzheimer's Disease and cognitive decline.Neurobiology of stress · 2024Article
- Screens in aging-relevant human ALS-motor neurons identify MAP4Ks as therapeutic targets for the disease.Cell death & disease · 2024Article
- 3D bioprinting patient-derived induced pluripotent stem cell models of Alzheimer's disease using a smart bioink.Bioelectronic medicine · 2023Article
- Chemical Replacement of Noggin with Dorsomorphin Homolog 1 for Cost-Effective Direct Neuronal Conversion.Cellular reprogramming · 2022Article
- Cell models for Down syndrome-Alzheimer's disease research.Neuronal signaling · 2022Review
- Macrophage Infiltration Reduces Neurodegeneration and Improves Stroke Recovery after Delayed Recanalization in Rats.Oxidative medicine and cellular longevity · 2022Article
- Article
- Medial septum tau accumulation induces spatial memory deficit via disrupting medial septum-hippocampus cholinergic pathway.Clinical and translational medicine · 2021Article
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4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAlzheimer's disease (AD) is an adult-onset mental disorder with aging as a major risk factor. Early and progressive degeneration of basal forebrain cholinergic neurons (BFCNs) contributes substantially to cognitive impairments of AD. An aging-relevant cell model of BFCNs will critically help understand AD and identify potential therapeutics. Recent studies demonstrate that induced neurons directly reprogrammed from adult human skin fibroblasts retain aging-associated features. However, human induced BFCNs (hiBFCNs) have yet to be achieved.
methodsWe examined a reprogramming procedure for the generation of aging-relevant hiBFCNs through virus-mediated expression of fate-determining transcription factors. Skin fibroblasts were obtained from healthy young persons, healthy adults and sporadic AD patients. Properties of the induced neurons were examined by immunocytochemistry, qRT-PCR, western blotting, and electrophysiology.
resultsWe established a protocol for efficient generation of hiBFCNs from adult human skin fibroblasts. They show electrophysiological properties of mature neurons and express BFCN-specific markers, such as CHAT, p75NTR, ISL1, and VACHT. As a proof-of-concept, our preliminary results further reveal that hiBFCNs from sporadic AD patients exhibit time-dependent TAU hyperphosphorylation in the soma and dysfunctional nucleocytoplasmic transport activities.
conclusionsAging-relevant BFCNs can be directly reprogrammed from human skin fibroblasts of healthy adults and sporadic AD patients. They show promises as an aging-relevant cell model for understanding AD pathology and may be employed for therapeutics identification for AD.
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