The modulatory role of early-life experiences and sex on cognitive resilience in APP/PS1 mice over time
- 1Amsterdam University Medical Center
Abstract
BACKGROUND: Cognitive resilience to Alzheimer's disease (AD) can be modelled in amyloid-expressing rodents through early handling (EH). This study investigated how EH and sex affect cognition and pathology over time. METHODS: We assessed cognition (Open field, Novel object recognition test, Barnes maze) in 6- and 12-month-old APP/PS1 and WT mice (N=180, EH/Ctrl X M/F), performed biochemical and histological analyses of several brain areas to assess effects on amyloid-beta, glial cells, and other markers of pathology, and investigated how behavior correlates with pathology. RESULTS: EH improved non-spatial memory at 6 months, consistent with a reduction of hippocampal microglia density, and normalized locomotor activity at 12 months (both p<0.05). Females demonstrated similar (6 & 12 months) or better (12 months) cognition, despite greater pathology across timepoints. Correlations implicated microglial recruitment in EH-related effects, supported by morphological analysis of prefrontal regions (p<0.05). CONCLUSION: Our findings highlight the critical role of early postnatal experiences and sex in shaping resilience in the context of AD pathology.
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BibTeX
@misc{carrigan2026modulatory,
title = {{The modulatory role of early-life experiences and sex on cognitive resilience in APP/PS1 mice over time}},
author = {M. Carrigan and J. Sanguino-Gomez and M. Bayer-Var and O. Minko and A. Bobkova and E. Ruzicka and L. Lopez-Fedjajeva and N. Renckens and L. Givalois and P. J. Lucassen and R. Ossenkoppele and H. J. Krugers},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.29.754953},
url = {https://www.biorxiv.org/content/10.64898/2026.09.29.754953v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - The modulatory role of early-life experiences and sex on cognitive resilience in APP/PS1 mice over time
AU - M. Carrigan
AU - J. Sanguino-Gomez
AU - M. Bayer-Var
AU - O. Minko
AU - A. Bobkova
AU - E. Ruzicka
AU - L. Lopez-Fedjajeva
AU - N. Renckens
AU - L. Givalois
AU - P. J. Lucassen
AU - R. Ossenkoppele
AU - H. J. Krugers
PY - 2026
DA - 2026/09/29
PB - bioRxiv
DO - 10.64898/2026.09.29.754953
UR - https://www.biorxiv.org/content/10.64898/2026.09.29.754953v1
AB - BACKGROUND: Cognitive resilience to Alzheimer's disease (AD) can be modelled in amyloid-expressing rodents through early handling (EH). This study investigated how EH and sex affect cognition and pathology over time. METHODS: We assessed cognition (Open field, Novel object recognition test, Barnes maze) in 6- and 12-month-old APP/PS1 and WT mice (N=180, EH/Ctrl X M/F), performed biochemical and histological analyses of several brain areas to assess effects on amyloid-beta, glial cells, and other markers of pathology, and investigated how behavior correlates with pathology. RESULTS: EH improved non-spatial memory at 6 months, consistent with a reduction of hippocampal microglia density, and normalized locomotor activity at 12 months (both p<0.05). Females demonstrated similar (6 & 12 months) or better (12 months) cognition, despite greater pathology across timepoints. Correlations implicated microglial recruitment in EH-related effects, supported by morphological analysis of prefrontal regions (p<0.05). CONCLUSION: Our findings highlight the critical role of early postnatal experiences and sex in shaping resilience in the context of AD pathology.
ER -