Direct conversion of fibroblast into neurons for Alzheimer's disease research: a systematic review
Open accessAbstract
Background: Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder without a cure. Innovative disease models, such as induced neurons (iNs), could enhance our understanding of AD mechanisms and accelerate treatment development. However, a review of AD human iN studies is necessary to consolidate knowledge. Objective: The objective of this review is to examine the current body of literature on AD human iN cells and provide an overview of the findings to date. Methods: We searched two databases for relevant studies published between 2010 and 2023, identifying nine studies meeting our criteria. Results: Reviewed studies indicate the feasibility of generating iNs directly from AD patients’ fibroblasts using chemical induction or viral vectors. These cells express mature neuronal markers, including MAP-2, NeuN, synapsin, and tau. However, most studies were limited in sample size and primarily focused on autosomal dominant familial AD (FAD) rather than the more common sporadic forms of AD. Several studies indicated that iNs derived from FAD fibroblasts exhibited abnormal amyloid-β metabolism, a characteristic feature of AD in humans. Additionally, elevated levels of hyperphosphorylated tau, another hallmark of AD, were reported in some studies. Conclusion: Although only a limited number of small-scale studies are currently available, AD patient-derived iNs hold promise as a valuable model for investigating AD pathogenesis. Future research should aim to conduct larger studies, particularly focusing on sporadic AD cases, to enhance the clinical relevance of the findings for the broader AD patient population. Moreover, these cells can be utilized in screening potential novel treatments for AD.
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Detecting the expression of Map-2 and NeuN helps determine the extent of neuronal damage and degeneration.
“Map-2 and NeuN are the neuronal marker proteins used to assess the morphology and function of neurons, and detecting the expression of Map-2 and NeuN could help know the extent of neuronal damage and degeneration in the present study (Götz and Ittner, 2008; Ghatak et al., 2019; Sattarov et al., 2023).”
From AD-Like Neuropsychiatric Dysfunction in a Mice Model Induced by a Combination of High-Fat Diet and Intraperitoneal Injection of Streptozotocin (2024) · cites this paper as Sattarov et al., 2023
The Results table lists MAP-2 and NeuN as markers of induced neurons. The Discussion (AD-related features in iN cells) reports that fewer MAP2-positive cells under APP overexpression may suggest decreased cell survival. It does not establish that measuring MAP-2 and NeuN together determines the extent of neuronal damage or degeneration; page numbers are unavailable in our copy. (LLM, conf=0.84)
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Cited by
Sorted by citations
Sun, H., Gao, X., Niu, J., Chen, P., He, S., Xu, S., & Ge, J. (2024) · eneuro · doi:10.1523/eneuro.0310-24.2024 · Cited by 12 · see citing works
- Authors
- Sattarov, R., Toresson, H., Orbjörn, C., & Mattsson-Carlgren, N.
- Affiliations
- Lund University (SE)
- Department of Clinical Sciences Malmö, Clinical Memory Research Unit, Lund University, Lund, Sweden
- Corresponding author
- Sattarov, Roman
- ORCID
- Sattarov, Roman
- Venue
- Journal of Alzheimer’s Disease
- Publisher
- SAGE Publications
- Published
- 2023-08-25
- Volume
- 95
- Issue
- 3
- Pages
- 805-828
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC10578293
- OpenAlex
- W4386245235
- Cited by
- 4
- References
- 15
- Citations by year
- 2025: 3 · 2024: 1
- FWCI
- 0.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Alzheimer s Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Australian Government
- Lunds Universitet
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse
- Sveriges Läkarförbund
- Skånes universitetssjukhus
- Marcus och Amalia Wallenbergs minnesfond
- Stiftelsen Bundy Academy
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- Alzheimer's disease, induced neurons
- MeSH terms
- Alzheimer Disease, Fibroblasts, Humans, Neurons, Amyloid beta-Peptides, tau Proteins
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