Direct Conversion of Fibroblast into Neurons for Alzheimer's Disease Research : A Systematic Review
Sattarov, Roman LU ; Toresson, Håkan LU ; Orbjörn, Camilla LU and Mattsson-Carlgren, Niklas LU
(2023)
In Journal of Alzheimer's Disease
95(3).
p.805-828
- Abstract
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... (More)
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.
(Less)
- author
- Sattarov, Roman
LU
; Toresson, Håkan
LU
; Orbjörn, Camilla
LU
and Mattsson-Carlgren, Niklas
LU
- organization
- publishing date
- 2023-09
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adult human dermal fibroblasts, Alzheimer's disease, amyloid-β, APOE, APP, familial Alzheimer's disease, human induced-neurons, sporadic Alzheimer's disease, tau
- in
- Journal of Alzheimer's Disease
- volume
- 95
- issue
- 3
- pages
- 24 pages
- publisher
- IOS Press
- external identifiers
-
- pmid:37661882
- scopus:85174033980
- ISSN
- 1387-2877
- DOI
- 10.3233/JAD-230119
- language
- English
- LU publication?
- yes
- id
- 64adde63-cb7a-4e66-8449-f749d2193aed
- date added to LUP
- 2023-12-11 15:07:40
- date last changed
- 2024-04-24 08:35:54
@article{64adde63-cb7a-4e66-8449-f749d2193aed,
abstract = {{<p>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.</p>}},
author = {{Sattarov, Roman and Toresson, Håkan and Orbjörn, Camilla and Mattsson-Carlgren, Niklas}},
issn = {{1387-2877}},
keywords = {{Adult human dermal fibroblasts; Alzheimer's disease; amyloid-β; APOE; APP; familial Alzheimer's disease; human induced-neurons; sporadic Alzheimer's disease; tau}},
language = {{eng}},
number = {{3}},
pages = {{805--828}},
publisher = {{IOS Press}},
series = {{Journal of Alzheimer's Disease}},
title = {{Direct Conversion of Fibroblast into Neurons for Alzheimer's Disease Research : A Systematic Review}},
url = {{http://dx.doi.org/10.3233/JAD-230119}},
doi = {{10.3233/JAD-230119}},
volume = {{95}},
year = {{2023}},
}