P014 - HUMAN AMYLOID SEEDS AGGREGATE MORE EFFICIENT THAN SEEDS FROM OLD 3XTG-AD MICE (ID 785)
- Juana Andreo-Lopez (Spain)
- Francisco Cantero Molina (Spain)
- Miriam Bettinetti-Luque (Spain)
- Kelly Huynh (United States of America)
- Marie Minh Thu Nguyen (United States of America)
- Alwin Cheung (United States of America)
- Janine Pham Tran (United States of America)
- Celia Da Cunha (United States of America)
- Laura Trujillo-Estrada (Spain)
- Cristina Nuñez-Diaz (Sweden)
- Alessandra Cadete Martini (United States of America)
- Stefania Forner (United States of America)
- Antonia Gutierrez (Spain)
- Frank LaFerla
- David Baglietto-Vargas (Spain)
Abstract
Aims
Most age-associated neurodegenerative disorders involve the aggregation of specific proteins within the nervous system, as occurs in Alzheimer’s disease (AD). Recent evidence indicates that Aβ can misfold and aggregate into seeds that structurally corrupt native proteins, mimicking a prion-like process of template protein corruption or seeding. In fact, studies in animal models show that the injection of brain homogenates from AD patients or from aged APP-transgenic mice containing Aβ aggregates, can induce some of the neuropathological hallmarks of AD. However, it is still unknown which Aβ-misfolded species are most efficient in triggering the aggregation process. Here, we seek to perform a comparative study to determine whether Aβ seeds from humans vs a familial AD line (the 3xTg-AD model) is more efficient to generate amyloid aggregates.
Methods
We employed histological and molecular approaches to determine amyloid level, species and aggregative capacity of brain homogenates from an AD patient (stage C for amyloid, from the Alzheimer’s Disease Research Center at UCI) vs old-3xTg-AD mice (25-month-old). Such brain homogenates were injected into the hippocampus of 7-month-old 3xTg-AD mice and the mice were analyzed at 18 months of age.
Results
Our findings demonstrated that amyloid seeds from the human patient have more capacity to generate Aβ plaques vs seeds from aged 3xTg-AD mice.
Conclusions
These results suggest that seeds from human patients seem to be more amyloidogenic than from aged 3xTg-AD mice. Thus, more profound understanding these factors will provide key insight on how amyloid pathology progress in AD.
