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Article

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

by
Chi Him Poon
1,
San Tung Nicholas Wong
1,
Jaydeep Roy
1,
Yingyi Wang
1,
Hui Wang Hujo Chan
1,
Harry Steinbusch
2,3,
Arjan Blokland
4,
Yasin Temel
2,5,
Luca Aquili
1,6 and
Lee Wei Lim
1,*
1
Neuromodulation Laboratory, School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
2
Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6211 LK Maastricht, The Netherlands
3
Department of Brain & Cognitive Sciences, Daegu Gyeongbuk Institute Science and Technology (DGIST), Daegu 42988, Republic of Korea
4
Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, 6211 LK Maastricht, The Netherlands
5
Department of Neurosurgery, Maastricht University Medical Centre, Maastricht University, 6211 LK Maastricht, The Netherlands
6
College of Health and Education, Discipline of Psychology, Murdoch University, Perth 6150, Australia
*
Author to whom correspondence should be addressed.
Cells 2023, 12(5), 780; https://doi.org/10.3390/cells12050780
Submission received: 27 January 2023 / Revised: 19 February 2023 / Accepted: 27 February 2023 / Published: 1 March 2023
(This article belongs to the Special Issue Current Approaches of Molecular and Biobehavioral Studies on Neuro-Psychiatric Diseases)
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Abstract

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.
Keywords: Alzheimer’s disease; cognition; amyloid plaque; neuronal loss; transgenic mouse models Alzheimer’s disease; cognition; amyloid plaque; neuronal loss; transgenic mouse models

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MDPI and ACS Style

Poon, C.H.; Wong, S.T.N.; Roy, J.; Wang, Y.; Chan, H.W.H.; Steinbusch, H.; Blokland, A.; Temel, Y.; Aquili, L.; Lim, L.W. 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. Cells 2023, 12, 780. https://doi.org/10.3390/cells12050780

AMA Style

Poon CH, Wong STN, Roy J, Wang Y, Chan HWH, Steinbusch H, Blokland A, Temel Y, Aquili L, Lim LW. 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. Cells. 2023; 12(5):780. https://doi.org/10.3390/cells12050780

Chicago/Turabian Style

Poon, Chi Him, San Tung Nicholas Wong, Jaydeep Roy, Yingyi Wang, Hui Wang Hujo Chan, Harry Steinbusch, Arjan Blokland, Yasin Temel, Luca Aquili, and Lee Wei Lim. 2023. "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" Cells 12, no. 5: 780. https://doi.org/10.3390/cells12050780

APA Style

Poon, C. H., Wong, S. T. N., Roy, J., Wang, Y., Chan, H. W. H., Steinbusch, H., Blokland, A., Temel, Y., Aquili, L., & Lim, L. W. (2023). 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. Cells, 12(5), 780. https://doi.org/10.3390/cells12050780

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