THE OFFSPRING OF MOTHERS HARBORING APP/PS1 MUTATIONS PRESENTS EARLY CHANGES IN BRAIN METABOLISM AND MEMORY

Abstract

Background: Previous studies suggested that individuals with a maternal history of Alzheimer’s Disease(AD) are at higher risk of developing AD than individuals with a paternal history of AD. One could suggest that intra-uterine interactions might be responsible for elevating this risk. In this context, AD rodent models are highly suited for improving our understanding of this matter since animals reach adulthood in a few months. Objective: Here, we aimed at investigating changes in memory-related processes and brain metabolism on the offspring born to transgenic mothers harboring human APP/PS1 mutations. Methods: Rats born to F344-AD(Tg-AD) and WT mothers were evaluated in two different time-points: ~5.5, and ~9.5 months. Y-maze test was used to evaluate spatial working memory and micro-PET [18F]FDG was used to assess brain glucose metabolism. Results: Y-maze test demonstrated that rats born to transgenic mothers presented memory disturbances, indexed by spontaneous alternation, at ~5.5 months and ~9.5 months (figure 1A), while rats born to WT mothers and Tg-AD fathers exhibited a decline in spontaneous alternation only at ~9.5 months. rats born to AD-Tg mothers present brain glucose hypermetabolism at ~9,5 months. Conclusion: Our findings demonstrate that rats born to AD-Tg mothers harboring APP/PS1 mutations present cognitive decline and brain glucose metabolism abnormalities earlier than those born to WT mothers. Further studies are needed to understand the biological basis behind this phenomenon.