Protein, peptide and mRNA levels and their correlation with aging in the APP23 mouse model for Alzheimer's disease
24 June 2016
Promotiezaal (UAntwerp, Campus Drie Eiken, Building Q) - Universiteitsplein 1 - 2610 Wilrijk (Antwerp)
4:00 PM - 6:00 PM
Peter Paul De Deyn, Debby Van Dam
PhD defence Leen Janssen - Department of Biomedical Sciences
The global population is aging. People are living longer and individuals over 60 years old represent an increasingly larger portion of the population. As a result, age-related diseases are expected to become one of the most prominent health care issues in the coming decades. Between 1990 and 2010 the disease burden caused by dementia more than doubled and no other disorder displays such a high correlation with aging. However, the aging factor is often neglected in dementia research, both in humans and in animal models. The most common cause of dementia is Alzheimer’s disease. In our research we, therefore, decided to investigate pathological changes and their correlation to aging in the APP23 mouse model for Alzheimer’s disease. The amyloid-beta peptide (Aβ) is believed to play a central role in AD pathology. After a thorough optimization and evaluation of the molecular, analytical techniques, we determined the levels of soluble Aβ and Aβ-producing proteins at various ages in our model. In addition, we used next generation RNA sequencing to examine age- and pathology-related gene expression changes and how they correlated with the observed changes in soluble Aβ levels. Our research demonstrated some of the limitations of the routine analytical techniques for the determination of Aβ levels, which should be taken into account in future analyses. In the APP23 model we observed two distinct phases in the life of these mice. On the one hand, we uncovered a developmental phase, which appears to mostly share features with FAD in young human carriers. On the other hand, we found an aging phase, which seems to model the progression of both FAD and SAD in humans. These findings will be crucial for the age selection and experimental design of future studies. In the end, we also identified several interesting molecular targets for further research, i.e. microglial activation, lysosomal degradation, neuron differentiation and the role of cytoskeletal regulation in these processes.