The modulatory role of early-life experiences and sex on cognitive resilience in APP/PS1 mice over time

Carrigan, M.; Sanguino-Gomez, J.; Bayer-Var, M.; Minko, O.; Bobkova, A.; Ruzicka, E.; Lopez-Fedjajeva, L.; Renckens, N.; Givalois, L.; Lucassen, P. J.; Ossenkoppele, R.; Krugers, H. J.

doi:10.64898/2026.09.29.754953

bioRxiv · 10.64898/2026.09.29.754953

The modulatory role of early-life experiences and sex on cognitive resilience in APP/PS1 mice over time

Carrigan, M.·Sanguino-Gomez, J.·Bayer-Var, M.·Minko, O.·Bobkova, A.·Ruzicka, E.·Lopez-Fedjajeva, L.·Renckens, N.·Givalois, L.·Lucassen, P. J.·Ossenkoppele, R.·Krugers, H. J.

View original source ↗Export metadata ↓

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.

Explore related subjects

animal behavior and cognition Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Carrigan, M., Sanguino-Gomez, J., Bayer-Var, M., Minko, O., Bobkova, A., Ruzicka, E., Lopez-Fedjajeva, L., Renckens, N., Givalois, L., Lucassen, P. J., Ossenkoppele, R., Krugers, H. J.. 2026-10-05. The modulatory role of early-life experiences and sex on cognitive resilience in APP/PS1 mice over time. https://doi.org/10.64898/2026.09.29.754953

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Behavioral divergence across replicated predation regimes is species-specific in two sympatric poeciliid fishes

Predation is a potent driver of behavioral divergence across prey populations, yet whether shared predation regimes generate similar responses in coexisting prey species remains unclear. Species differences in reproductive and foraging traits may alter vulnerability to predators, generating species-specific responses. We compared behavior and cognition of two poeciliid fishes (Gambusia affinis and Poecilia latipinna) that differ in body size, the presence of male ornamentation, and mating tactics. We sampled both species across replicate high- and low-predation regimes and measured exploration, shyness, boldness, social motivation, and detour solve latency (N = 509). Multivariate behavior and cognition differed between predation regimes, and the magnitude of divergence varied with species but not body size. Consistent with the multivariate pattern, the more conspicuous P. latipinna exhibited higher boldness and overall lower exploration under high-predation, while high- and low-predation populations of G. affinis did not differ. These findings suggest either that the more conspicuous species experiences greater predation risk or that the less conspicuous species reduces its predation risk through alternative phenotypic responses. More broadly, species differences in reproductive phenotypes associated with sexual selection may help explain why shared predation regimes generate variable patterns of behavioral divergence across taxa.

animal behavior and cognition↗

bioRxiv2026

Capturing the rhythm: methodological choices shape inference from circadian activity data

Abstract 1. Statistical tools and analytical decisions for analysing animal activity data are often limited and poorly justified, particularly with respect to model choice, sampling design and temporal aggregation. These shortcomings can constrain our ability to draw accurate and biologically meaningful inferences about behaviour. 2. We interrogated 24 h activity data taken from individual males and females derived from five Drosophila melanogaster populations to generate a general framework for collecting and analysing activity data that systematically compares common model classes, continuous verses fragmented sampling strategies, and alternative temporal aggregation choices (time-bin sizes). 3. Our analyses identified generalised additive mixed models (GAMMs) applied to high-frequency continuous data with small-moderate bin sizes (1-5 minutes) as providing the most robust and interpretable inference for our complex, high-frequency activity data. 4. However, our interrogation of the data set confirmed that analytical and sampling decisions need to be tailored to the study species, the timing of activities and the nature of the behaviour of interest. Accordingly, polynomial and cosinor generalised linear models, increased but biologically targeted snapshot sampling, and bin sizes smaller than one hour yielded adequate analyses with similar biological conclusions when appropriately matched to the system. 5. Our approach provides an accessible decision-making framework for activity analyses that allows researchers across behavioural, ecological and evolutionary studies to justify and optimise choices about data collection and modelling. Such an approach improves the biological relevance of inference and supporting the use of modern tracking and analytical technologies.

animal behavior and cognition↗

bioRxiv2026

Greylag geese (Anser anser) initiate group flight based on the number and identities of callers

Social animals need to maintain cohesion when they move, and movement decisions are influenced by social organization and ecological or individual needs. To maintain synchrony during collective movement, the use of signals, including vocal signals, is often necessary. Greylag geese are gregarious and vocal before and during flight. We observed instances of naturally occurring flight initiation attempts in a free-living population of greylag geese -n = 133 birds- to investigate the decision-making process in this species, including the role vocalisations play in flight decisions. We recorded the number of participants in flight-initiation attempts, their vocal behaviour -using two call types specific to flight initiation signalling: Locomotion and Pre-flight calls-, the outcome of those attempts, in addition to the resulting flying group size and composition. We found that the identities and number of flock members joining in the calling chorus predicted both the probability of successful flight and the resulting flying group size. The number of Locomotion callers was associated with an increased probability of success, as well as larger flying group size, including both family and non-family fliers. The number of Pre-flight callers was also associated with a higher probability of successful flight, but its effect on the increase in flying group size was marginal. Successful departures were more probable when the family members of the initiator responded vocally. Overall, our findings are consistent with a system where the decision to fly is made individually using two distinct vocal signals to estimate the number of voters and at least the identities of social partners and progeny. In species where temporal and spatial group cohesion varies both seasonally and diurnally, individuals priorities appear to be maintaining proximity to mates and family members, followed by maximizing the size of flight groups.

animal behavior and cognition↗