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

C.H. Poon; San Tung Nicholas Wong; Jaydeep Roy; Yingyi Wang; Hui Wang Hujo Chan; Harry Steinbusch; A. Blokland; Y. Temel; Luca Aquili; Lee Wei Lim

doi:10.3390/cells12050780

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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

Journal article

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Peer reviewed

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

C.H. Poon, San Tung Nicholas Wong, Jaydeep Roy, Yingyi Wang, Hui Wang Hujo Chan, Harry Steinbusch, A. Blokland, Y. Temel, Luca Aquili and Lee Wei Lim

Cells (Basel, Switzerland), Vol.12(5), Art. 780

2023

DOI: https://doi.org/10.3390/cells12050780

PMID: 36899916

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Abstract

Alzheimer Disease - pathology

Amyloid

Amyloid beta-Peptides

Amyloid beta-Protein Precursor

Animals

Female

Male

Mice

Mice, Transgenic

Plaque, Amyloid - pathology

Sex Characteristics

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.

Details

Title: 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
Authors/Creators: C.H. Poon - Neuromodulation Laboratory, School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
San Tung Nicholas Wong - Neuromodulation Laboratory, School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
Jaydeep Roy - Neuromodulation Laboratory, School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
Yingyi Wang - Neuromodulation Laboratory, School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
Hui Wang Hujo Chan - Neuromodulation Laboratory, School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
Harry Steinbusch - Department of Brain & Cognitive Sciences, Daegu Gyeongbuk Institute Science and Technology (DGIST), Daegu 42988, Republic of Korea
A. Blokland - Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, 6211 LK Maastricht, The Netherlands
Y. Temel - Department of Neurosurgery, Maastricht University Medical Centre, Maastricht University, 6211 LK Maastricht, The Netherlands
Luca Aquili
Lee Wei Lim - Neuromodulation Laboratory, School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
Publication Details: Cells (Basel, Switzerland), Vol.12(5), Art. 780
Publisher: MDPI
Identifiers: 991005562369807891
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article
Note: This article belongs to the Special Issue Current Approaches of Molecular and Biobehavioral Studies on Neuro-Psychiatric Diseases

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.52 Neurodegenerative Diseases; 1.52.57 Alzheimer's Mechanisms
Web Of Science research areas: Cell Biology
ESI research areas: Biology & Biochemistry