Sex Differences between Neuronal Loss and the Early Onset of Amyloid Deposits and Behavioral Consequences in 5xFAD Transgenic Mouse as a Model for Alzheimer's Disease

Chi Him Poon, San Tung Nicholas Wong, Jaydeep Roy, Yingyi Wang, Hui Wang Hujo Chan, Harry Steinbusch, Arjan Blokland, Yasin Temel, Luca Aquili, Lee Wei Lim*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


A promising direction in the research on Alzheimer's Disease (AD) is the identification of biomarkers that better inform the disease progression of AD. However, the performance of amyloid-based biomarkers in predicting cognitive performance has been shown to be suboptimal. We hypothesise that neuronal loss could better inform cognitive impairment. We have utilised the 5xFAD transgenic mouse model that displays AD pathology at an early phase, already fully manifested after 6 months. We have evaluated the relationships between cognitive impairment, amyloid deposition, and neuronal loss in the hippocampus in both male and female mice. We observed the onset of disease characterized by the emergence of cognitive impairment in 6-month-old 5xFAD mice coinciding with the emergence of neuronal loss in the subiculum, but not amyloid pathology. We also showed that female mice exhibited significantly increased amyloid deposition in the hippocampus and entorhinal cortex, highlighting sex-related differences in the amyloid pathology of this model. Therefore, parameters based on neuronal loss might more accurately reflect disease onset and progression compared to amyloid-based biomarkers in AD patients. Moreover, sex-related differences should be considered in studies involving 5xFAD mouse models.

Original languageEnglish
Article number780
Number of pages15
Issue number5
Publication statusPublished - Mar 2023


  • Female
  • Mice
  • Male
  • Animals
  • Alzheimer Disease/pathology
  • Mice, Transgenic
  • Amyloid beta-Protein Precursor
  • Amyloid beta-Peptides
  • Plaque, Amyloid/pathology
  • Sex Characteristics
  • Amyloid

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