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.
| Original language | English |
|---|---|
| Pages (from-to) | 490-495 |
| Number of pages | 6 |
| Journal | NeuroImage |
| Volume | 184 |
| DOIs | |
| Publication status | E-pub ahead of print - 2018 |
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Exploring Alzheimer's disease mouse brain through X-ray phase contrast tomography : From the cell to the organ. / Massimi, Lorenzo; Bukreeva, Inna; Santamaria, Giulia; Fratini, Michela; Corbelli, Alessandro; Brun, Francesco; Fumagalli, Stefano; Maugeri, Laura; Pacureanu, Alexandra; Cloetens, Peter; Pieroni, Nicola; Fiordaliso, Fabio; Forloni, Gianluigi; Uccelli, Antonio; Kerlero de Rosbo, Nicole; Balducci, Claudia; Cedola, Alessia.
In: NeuroImage, Vol. 184, 2018, p. 490-495.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Exploring Alzheimer's disease mouse brain through X-ray phase contrast tomography
T2 - From the cell to the organ
AU - Massimi, Lorenzo
AU - Bukreeva, Inna
AU - Santamaria, Giulia
AU - Fratini, Michela
AU - Corbelli, Alessandro
AU - Brun, Francesco
AU - Fumagalli, Stefano
AU - Maugeri, Laura
AU - Pacureanu, Alexandra
AU - Cloetens, Peter
AU - Pieroni, Nicola
AU - Fiordaliso, Fabio
AU - Forloni, Gianluigi
AU - Uccelli, Antonio
AU - Kerlero de Rosbo, Nicole
AU - Balducci, Claudia
AU - Cedola, Alessia
N1 - Copyright © 2018. Published by Elsevier Inc.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
U2 - 10.1016/j.neuroimage.2018.09.044
DO - 10.1016/j.neuroimage.2018.09.044
M3 - Article
VL - 184
SP - 490
EP - 495
JO - NeuroImage
JF - NeuroImage
SN - 1053-8119
ER -