AMYCHRON – Amyloid Chronology to Understand Aβ Pathogenicity in Alzheimers disease

It is of critical importance to our understanding of Alzheimer’s disease (AD) pathology, to determine how key pathological factors including beta-amyloid (Aβ) plaque formation are interconnected and implicated in nerve cell death, clinical symptoms and disease progression.

Exactly how Aβ plaques begin, proceed and initiate subsequent neurotoxic mechanisms is not well understood.The primary aim of this research is to follow Aβ plaque formation dynamics in AD mouse models and AD patient brain biopsies and post mortem brain tissue.

For this, we pioneered novel chemical imaging tools that allow to delineate spatial protein turnover kinetics in the brain that do reflect in vivo Aβ build up and deposition.

With these tools we will track the earliest seeds of Aβ deposition through ongoing plaque development along with spatial gene expression analysis.This will help to address the following major questions in this proposal: (a) Where and When, within or outside nerve cells are different Aβ structuresformed? (b) What is the sequence of evolving plaque pathology as well as downstream synaptic changes and Tau pathology? and (c) How are these observations translated to human AD pathogenesis.

This will bring considerable novel information about the deposition mechanism of Aβ and its toxic interactions with the surrounding and open up for novel tailored strategies to target AD pathology as well as to develop new AD biomarkers.