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Peer-reviewedCC BYJournal of Neurochemistry

Limitations and Strengths of the SH ‐ SY5Y Neuroblastoma Cell Line as a Model of β‐Amyloid Neurotoxicity: Lessons From a Systematic Review and Meta‐Analysis

  • Nathalia Reges Pinheiro1,2
  • Clarissa F. D. Carneiro1,3
  • Giulia Scarcella Cancelliero1,2
  • Giovanna Orlovski Nogueira2
  • Glaucia Maria de Almeida2
  • Nathalia Fernandes1,4,5,6
  • Ana Paula Wasilewska‐Sampaio7
  • Samantha M. Martins8
  • Antônio Felix da Silva Filho1,9
  • Olavo B. Amaral1,3
  • Adriano Silva Sebollela1,2
9 affiliations
  1. 1Brazilian Reproducibility Initiative in preclinical Systematic review and meta-Analysis (BRISA), Brazil
  2. 2Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil
  3. 3Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
  4. 4Institute of Biological Sciences, Federal University of Amazonas, Manaus, AM, Brazil
  5. 5Laboratory for Sustainability and Technology in Mountain Regions, Campus of Santa Apolónia, Polytechnic Institute of Bragança, Portugal
  6. 6Mountain Research Center, Campus of Santa Apolónia, Polytechnic Institute of Bragança, Bragança, Portugal
  7. 7Brazilian Biosciences National Laboratory (LNBio), Brazilian Centre for Research in Energy and Materials (CNPEM), SP, Brazil
  8. 8Laboratório de Produtos Bioativos, Federal University of Rio de Janeiro, Campus Macaé, Macaé, RJ, Brazil
  9. 9Department of Medicine, University of Pernambuco, Garanhuns, PE, Brazil
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Abstract

The SH‐SY5Y human neuroblastoma cell line is widely used as an in vitro model of β‐amyloid (Aβ) neurotoxicity in Alzheimer's disease (AD). However, the lack of standardized protocols for assessing Aβ toxicity—including differentiation strategies for SH‐SY5Y cells—limits the comparability of results across studies. To address these issues, we conducted a systematic review and meta‐analysis to evaluate how methodological factors influence Aβ‐induced toxicity in SH‐SY5Y cells. We included 359 eligible studies encompassing 1192 MTT‐based comparisons of cell viability between Aβ‐treated and control SH‐SY5Y cells. A three‐level meta‐analysis estimated mean cell viability after Aβ exposure at 63% of control levels (95% CI [61.6; 64.3]), with very high heterogeneity ( I 2 = 99.6%). Meta‐regression identified significant associations between increased toxicity and higher Aβ concentrations, longer exposure durations, and the use of peptide preparations described as fibrils. Conversely, differentiation protocols, duration, and cell density did not significantly influence toxicity outcomes. Reporting quality was often poor, with frequent omissions regarding cell line origin, authentication, contamination testing, Aβ preparation details, and nature of the experimental unit. Overall, our findings show robust Aβ toxicity in SH‐SY5Y cells, primarily driven by dose, exposure time, and Aβ aggregation state, but not cell differentiation status. Our conclusions highlight the critical need for better reporting of Aβ exposure parameters to enhance reproducibility and translational potential in AD research. image

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Cite

BibTeXRIS
BibTeX
@article{pinheiro2026limitations,
  title = {{Limitations and Strengths of the SH ‐ SY5Y Neuroblastoma Cell Line as a Model of β‐Amyloid Neurotoxicity: Lessons From a Systematic Review and Meta‐Analysis}},
  author = {Nathalia Reges Pinheiro and Clarissa F. D. Carneiro and Giulia Scarcella Cancelliero and Giovanna Orlovski Nogueira and Glaucia Maria de Almeida and Nathalia Fernandes and Ana Paula Wasilewska‐Sampaio and Samantha M. Martins and Antônio Felix da Silva Filho and Olavo B. Amaral and Adriano Silva Sebollela},
  journal = {Journal of Neurochemistry},
  year = {2026},
  month = jul,
  doi = {10.1111/jnc.70523},
  url = {https://doi.org/10.1111/jnc.70523},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Limitations and Strengths of the SH ‐ SY5Y Neuroblastoma Cell Line as a Model of β‐Amyloid Neurotoxicity: Lessons From a Systematic Review and Meta‐Analysis
AU  - Nathalia Reges Pinheiro
AU  - Clarissa F. D. Carneiro
AU  - Giulia Scarcella Cancelliero
AU  - Giovanna Orlovski Nogueira
AU  - Glaucia Maria de Almeida
AU  - Nathalia Fernandes
AU  - Ana Paula Wasilewska‐Sampaio
AU  - Samantha M. Martins
AU  - Antônio Felix da Silva Filho
AU  - Olavo B. Amaral
AU  - Adriano Silva Sebollela
PY  - 2026
DA  - 2026/07/01
JO  - Journal of Neurochemistry
DO  - 10.1111/jnc.70523
UR  - https://doi.org/10.1111/jnc.70523
AB  - The SH‐SY5Y human neuroblastoma cell line is widely used as an in vitro model of β‐amyloid (Aβ) neurotoxicity in Alzheimer's disease (AD). However, the lack of standardized protocols for assessing Aβ toxicity—including differentiation strategies for SH‐SY5Y cells—limits the comparability of results across studies. To address these issues, we conducted a systematic review and meta‐analysis to evaluate how methodological factors influence Aβ‐induced toxicity in SH‐SY5Y cells. We included 359 eligible studies encompassing 1192 MTT‐based comparisons of cell viability between Aβ‐treated and control SH‐SY5Y cells. A three‐level meta‐analysis estimated mean cell viability after Aβ exposure at 63% of control levels (95% CI [61.6; 64.3]), with very high heterogeneity ( I 2 = 99.6%). Meta‐regression identified significant associations between increased toxicity and higher Aβ concentrations, longer exposure durations, and the use of peptide preparations described as fibrils. Conversely, differentiation protocols, duration, and cell density did not significantly influence toxicity outcomes. Reporting quality was often poor, with frequent omissions regarding cell line origin, authentication, contamination testing, Aβ preparation details, and nature of the experimental unit. Overall, our findings show robust Aβ toxicity in SH‐SY5Y cells, primarily driven by dose, exposure time, and Aβ aggregation state, but not cell differentiation status. Our conclusions highlight the critical need for better reporting of Aβ exposure parameters to enhance reproducibility and translational potential in AD research. image
SN  - 0022-3042
SN  - 1471-4159
ER  -