The potential link between the infections and the development of Alzheimer's disease (AD) has led to speculations about the role of various pathogens in triggering amyloid-β (Aβ) overproduction, possibly leading to AD onset. The globally distributed dog roundworm Toxocara canis was suggested to be a suitable candidate due to neurotropism of the larvae and infection chronicity. This study investigated whether chronic T. canis infection induces AD-like pathology in mice and whether Aβ is toxic to T. canis. BALB/c and APP/PS1 transgenic mice, which overproduce Aβ, were infected with T. canis L3 larvae and monitored for larval burden, Aβ accumulation, and behavioral changes. In vitro tests of recombinant Aβ toxicity against the larvae were also performed. Despite the presence of T. canis larvae in the central nervous system 8 and 16 weeks post-infection, no significant increase in Aβ concentration or AD-related behavioral alterations were observed. Aβ was detected on the surface and within the intestines of T. canis larvae, but in vitro exposure to recombinant Aβ did not affect larval viability or morphology. Our findings suggest that T. canis infection does not trigger AD-like pathology in mice, and Aβ does not act as an antiparasitic agent. This challenges the emerging hypothesis that chronic neurotoxocarosis infections may contribute to AD development.

TITLE: Absence de preuve de pathologie de la maladie d’Alzheimer chez les souris infectées par Toxocara canis. ABSTRACT: Le lien potentiel entre les infections et le développement de la maladie d’Alzheimer (MA) a suscité des spéculations sur le rôle de divers agents pathogènes dans le déclenchement de la surproduction de β-amyloïde (βA), pouvant conduire à l’apparition de la MA. Toxocara canis, un nématode du chien, répandu mondialement, a été suggéré comme un candidat potentiel en raison du neurotropisme de ses larves et de la chronicité de son infection. Cette étude examine si une infection chronique à T. canis induit une pathologie de type MA chez la souris et si la βA est toxique pour T. canis. Des souris transgéniques BALB/c et APP/PS1, qui surproduisent la βA, ont été infectées par des larves L3 de T. canis et la charge larvaire, l’accumulation de βA et les changements comportementaux ont été étudiés. Des tests in vitro de toxicité de la βA recombinante contre les larves ont également été réalisés. Malgré la présence de larves de T. canis dans le système nerveux central 8 et 16 semaines après l’infection, aucune augmentation significative de la concentration de la βA ni d’altération comportementale liée à la MA n’ont été observées. La βA a été détectée à la surface et dans les intestins des larves de T. canis, mais l’exposition in vitro à la βA recombinante n’a pas affecté la viabilité ou la morphologie des larves. Nos résultats suggèrent que l’infection à T. canis ne déclenche pas de pathologie de type MA chez la souris, et que la βA n’agit pas comme agent antiparasitaire. Cela remet en cause l’hypothèse émergente selon laquelle les infections chroniques par neurotoxocarose pourraient contribuer au développement de la MA.

Department of Parasitology Faculty of Science Charles University Viničná 7 Prague 2 12844 Czechia

Department of Parasitology Faculty of Science Charles University Viničná 7 Prague 2 12844 Czechia Department of Biochemical Sciences Faculty of Pharmacy in Hradec Králové Charles University Akademika Heyrovského 1203 Hradec Králové 50005 Czechia

Institute of Medical Microbiology 1st Faculty of Medicine Charles University and General University Hospital Prague Studničkova 7 Prague 2 12800 Czechia

Laboratory of Neurophysiology of Memory Institute of Physiology Czech Academy of Sciences Vídeňská 1083 Prague 4 14200 Czechia

Sleep and Chronobiology Research Centre National Institute of Mental Health Topolová 748 Klecany 25067 Czechia

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