The influence of soluble amyloid β on resting state functional connectivity in the absence or presence of amyloid β plaques.

Alzheimer's disease (AD) is a devastating neurological disorder and the most common type of dementia in the elderly population. It is mainly characterised by the appearance of small protein aggregates inside the brain, commonly known as amyloid beta (Aβ) plaques. These Aβ plaques form when soluble Aβ peptides oligomerize, a process which was found to occur more frequently when high concentrations of soluble Aβ are present. During preliminary studies in transgenic AD mice, we have observed that the strength of functional connectivity (FC) between brain regions initially increases. During the period of intense Aβ plaque formation however, FC decreases. These results postulated a dynamic rewiring of the brains' connections to adapt to high concentrations of soluble Aβ and Aβ plaque formation. In this project, we wish untangle the influence of soluble Aβ on resting state functional connectivity in the presence or absence of Aβ plaques. We will make use of the Tet-Off APP mouse model which allows inducible over-expression of the amyloid precursor protein by means of doxycycline treatment. We will use Rs fMRI to longitudinally follow up changes in FC between different brain regions due to this controlled over-expression of amyloid precursor protein. The results of this research will allow a better understanding of how the brain adapts to progressive amyloidosis and how both clinicians and researchers should interpret AD Rs fMRI data.

Keywords:BIO-IMAGING

Disciplines:Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing