Fisher Center scientists visualise brain defects that cause Alzheimer's disease

The Fisher Center for Alzheimer's Research Foundation is proud to announce that they have funded the conception of state-of-the-art technology created by its scientists

As published in the scientific journal Cell Reports, under the direction of Dr Paul Greengard, Dr Marc Tessier-Lavigne and spearheaded by Dr Marc Flajolet, Fisher Center scientists have created technology that allows the visualisation of amyloid plaques as well as other Alzheimer's hallmarks, such as tau, vasculature and microglia activation, in a large volume, in an entire mouse brain with the potential application of frozen human brain samples.

‘We are proud that the funding we provide has resulted in innovative, never before seen imaging of what causes Alzheimer's disease,’ said Kent L. Karosen, President/CEO Fisher Center for Alzheimer's Research Foundation. The Fisher Center scientists are working diligently to better understand the cause and cure of the disease and, with the ability to visualise the causes of Alzheimer's, we're one step closer to a cure.’

Using the iDISCO visualisation method involving targeted molecular labelling, tissue clearing and light-sheet microscopy, the Fisher Center scientists gained unprecedented access to intact Alzheimer's disease mouse brains and studied, in detail, amyloid plaque content in five major brain regions at different ages.

The scientists are now also able to covisualise amyloid plaques in 3D together with two other parameters (such as tau, microglia and vasculature). Volume imaging coupled with automated detection and mapping enables precise and fast quantification of plaques within the entire intact mouse brain, a much faster and more economical alternative to standard beta amyloid plaque labelling.

Further analysis of archived human brain tissues from patients led to the remarkable discovery of very large three-dimensional amyloid patterns that the researchers of the Fisher Center called three-dimensional amyloid patterns (TAPs) and that measure up to 27m3. In these human samples, contrary to the mouse brains, scientists also observed a larger diversity of the amyloid plaques in terms of size and three-dimensional shape.

These intriguing differences between animal models and human samples might highlight a novel trait of, and specific to, the development of Alzheimer's disease in humans. The combination of these parameters provides access to an expansive set of possibilities for preclinical studies and for further pathological exploration. Larger studies focusing on patient samples will allow scientists to confirm the existence of TAPs and retrospective studies performed with clinicians might lead to the emergence of a disease classification.