Exploring Alzheimer's disease mouse brain through X-ray phase contrast tomography: From the cell to the organ

Publication date: Available online 18 September 2018

Source: NeuroImage

Author(s): Lorenzo Massimi, Inna Bukreeva, Giulia Santamaria, Michela Fratini, Alessandro Corbelli, Francesco Brun, Stefano Fumagalli, Laura Maugeri, Alexandra Pacureanu, Peter Cloetens, Nicola Pieroni, Fabio Fiordaliso, Gianluigi Forloni, Antonio Uccelli, Nicole Kerlero de Rosbo, Claudia Balducci, Alessia Cedola

Abstract

Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disorder associated with aberrant production of beta-amyloid (Aβ) peptide depositing in brain as amyloid plaques. While animal models allow investigation of disease progression and therapeutic efficacy, technology to fully dissect the pathological mechanisms of this complex disease at cellular and vascular levels is lacking.

X-ray phase contrast tomography (XPCT) is an advanced non-destructive 3D multi-scale direct imaging from the cell through to the whole brain, with exceptional spatial and contrast resolution. We exploit XPCT to simultaneously analyse disease-relevant vascular and neuronal networks in AD mouse brain, without sectioning and staining. The findings clearly show the different typologies and internal structures of Aβ plaques, together with their interaction with patho/physiological cellular and neuro-vascular microenvironment. XPCT enables for the first time a detailed visualization of amyloid-angiopathy at capillary level, which is impossible to achieve with other approaches.

XPCT emerges as added-value technology to explore AD mouse brain as a whole, preserving tissue chemistry and structure, enabling the comparison of physiological vs. pathological states at the level of crucial disease targets. In-vivo translation will permit to monitor emerging therapeutic approaches and possibly shed new light on pathological mechanisms of neurodegenerative diseases.

Graphical abstract

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