Noninvasive Magnetic Resonance Imaging Detection of Cerebral Amyloid Angiopathy-Related Microvascular Alterations Using Superparamagnetic Iron Oxide Particles in APP Transgenic Mouse Models of Alzheimer's Disease: Application to Passive Aβ Immunotherapy

Beckmann, Nicolau; Gérard, Christelle; Abramowski, Dorothée; Cannet, Catherine; Staufenbiel, Matthias

doi:10.1523/jneurosci.4936-10.2011

Cited by 63 publications

(51 citation statements)

References 39 publications

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“…We found no accumulation of the SPIONs in blood vessels. This is consistent with the small size of the SPIONs used and the fact that Beckmann et al [75] have found no detectable cerebral amyloid angiopathy or MRI-detectable lesions in singly-transgenic AβPP mice for mice less than 15 months of age. Our mice were only 14 months old when killed for this study.…”

Section: Discussionsupporting

confidence: 83%

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SPION-Enhanced Magnetic Resonance Imaging of Alzheimer's Disease Plaques in AβPP/PS-1 Transgenic Mouse Brain

Sillerud

Solberg

Chamberlain

et al. 2013

JAD

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In our program to develop non-invasive magnetic resonance imaging (MRI) methods for the diagnosis of Alzheimer’s disease (AD), we have synthesized antibody-conjugated, superparamagnetic iron oxide nanoparticles (SPIONs) for use as an in vivo agent for MRI detection of amyloid-β plaques in AD. Here we report studies in AβPP/PS1 transgenic mice, which demonstrate the ability of novel anti-AβPP conjugated SPIONs to penetrate the blood-brain barrier to act as a contrast agent for MR imaging of plaques. The conspicuity of the plaques increased from an average Z-score of 5.1 ± 0.5 to 8.3 ± 0.2 when the plaque contrast to noise ratio was compared in control AD mice with AD mice treated with SPIONs. The number of MRI-visible plaques per brain increased from 347 ± 45 in the control AD mice, to 668 ± 86 in the SPION treated mice. These results indicated that our SPION enhanced amyloid-β detection method delivers an efficacious, non-invasive MRI detection method in transgenic mice.

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Section: Discussionsupporting

confidence: 83%

“…1H). We were initially surprised by this result because amyloid plaques are known to contain iron [74], but several investigators have found [21, 31, 74, 75] that simple Perl’s staining, without DAB enhancement, does not reveal the small amount of iron present in the cortical plaques from transgenic PS1/AβPP mice.…”

Section: Resultsmentioning

confidence: 99%

SPION-Enhanced Magnetic Resonance Imaging of Alzheimer's Disease Plaques in AβPP/PS-1 Transgenic Mouse Brain

Sillerud

Solberg

Chamberlain

et al. 2013

JAD

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“…However, the detection of CAA-related alterations in the microvasculature remains crucial for the evaluation of therapies. A previous study clearly showed that passive β-amyloid immunotherapy in APP23 mice amplified microhemorrhages throughout the entire brain 34 . In our study, we showed that high-resolution gre3D anatomical MRI at 7 T is sensitive enough for the detection of cerebral microhemorrhages without contrast agents.…”

Section: Discussionmentioning

confidence: 90%

Longitudinal PET-MRI reveals β-amyloid deposition and rCBF dynamics and connects vascular amyloidosis to quantitative loss of perfusion

Maier

Wehrl

Schmid

et al. 2014

Nat Med

114

110

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The dynamics of β-amyloid deposition and related second-order physiological effects, such as regional cerebral blood flow (rCBF), are key factors for a deeper understanding of Alzheimer's disease (AD). We present longitudinal in vivo data on the dynamics of β-amyloid deposition and the decline of rCBF in two different amyloid precursor protein (APP) transgenic mouse models of AD. Using a multiparametric positron emission tomography and magnetic resonance imaging approach, we demonstrate that in the presence of cerebral β-amyloid angiopathy (CAA), β-amyloid deposition is accompanied by a decline of rCBF. Loss of perfusion correlates with the growth of β-amyloid plaque burden but is not related to the number of CAA-induced microhemorrhages. However, in a mouse model of parenchymal β-amyloidosis and negligible CAA, rCBF is unchanged. Because synaptically driven spontaneous network activity is similar in both transgenic mouse strains, we conclude that the disease-related decline of rCBF is caused by CAA.

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“…For the above study, MNPs were injected i.v. to transgenic AD mice, after 24 h of administration these particles were taken up by macrophages and attenuation of MRI signals increased the detectability of the lesions in AD mice [53]. Detecting such events in vivo can facilitate understanding of the role of CAA in dementia development.…”

Section: Theranostic Approach Of Mnps For Neurodegenerative Diseasementioning

confidence: 99%

Therapeutic approaches of magnetic nanoparticles for the central nervous system

Dilnawaz

Sahoo

2015

Drug Discovery Today

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Noninvasive Magnetic Resonance Imaging Detection of Cerebral Amyloid Angiopathy-Related Microvascular Alterations Using Superparamagnetic Iron Oxide Particles in APP Transgenic Mouse Models of Alzheimer's Disease: Application to Passive Aβ Immunotherapy

Abstract: Cerebral amyloid angiopathy (CAA) is a common feature of Alzheimer's disease (AD).

Cited by 63 publications

References 39 publications

SPION-Enhanced Magnetic Resonance Imaging of Alzheimer's Disease Plaques in AβPP/PS-1 Transgenic Mouse Brain

SPION-Enhanced Magnetic Resonance Imaging of Alzheimer's Disease Plaques in AβPP/PS-1 Transgenic Mouse Brain

Longitudinal PET-MRI reveals β-amyloid deposition and rCBF dynamics and connects vascular amyloidosis to quantitative loss of perfusion

Therapeutic approaches of magnetic nanoparticles for the central nervous system

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