The Search - Alzheimer’s Disease

An in vivo study in transgenic mice of Alzheimer’s disease

Speakers: Steffen Burgold and Finn Peters from German Center for Neurodegenerative Diseases

Abstract: Alzheimer’s disease (AD) is the most common form of dementia with nearly 44 million people affected worldwide. Characteristic neuropathological hallmarks of the disease are β-amyloid plaques which result from abnormal protein aggregation and deposition of β-amyloid peptide (Aβ). Aβ is produced by cleavage of the amyloid precursor protein. The amyloid-cascade-hypothesis postulates, based on strong genetic evidences, that Aβ accumulation is the central event in the etiology of AD.

Here we use long-term in vivo two-photon imaging to investigate the dynamics of β-amyloid plaque genesis and growth in transgenic mouse models of Alzheimer’s disease. A fluorescent dye is used to stain β-amyloid plaques in vivo and repeated injections enable us to follow plaque formation as well as their growth kinetics. In order to assess the size of β-amyloid plaques over time we established image analysis protocols to extract quantitative data from the high resolution four dimensional datasets.

The results from our study in mice showed sigmoid-shaped growth kinetics similar to those found in humans with a familiar record of Alzheimer’s disease by applying a β-amyloid radioactive tracer in combination with positron emission tomography imaging. We hope this work will help testing therapeutic strategies for Alzheimer’s disease in animal models and translating them to the human situation.

What will you learn?

• Recent findings in Alzheimer's disease therapy
• New methods of testing efficacy of Alzheimer's therapies in preclinical studies
• Image analysis protocol for assessing the growth of β-amyloid plaques over time