IC‐P‐064: Tau immunotherapy improves axonal transport as detected <i>in vivo</i> by manganese‐enhanced magnetic resonance imaging

Little, Benjamin; Khan, Umer; Bertrand, Anne; Rajamohamedsait, Hameetha B.; Hill, Lindsay; Hoang, Dung Minh; Wadghiri, Youssef Zaim; Sigurdsson, Einar M.

doi:10.1016/j.jalz.2012.05.097

Cited by 2 publications

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“…Manganese Enhanced MRI (MEMRI) utilizes divalent manganese, Mn 2+ , which enters activated neurons through calcium channels and produces a strong signal enhancement on T1-weighted MRI [25;26]. MEMRI is also emerging as an effective in vivo approach for tracing axonal tracts [26], showing T1-weighted-MRI enhancement in the adult and developing mouse brain after subcutaneous, intraperitoneal or intranasal injection of MnCl 2 [27–30]. Initial concerns about neurotoxic effects of manganese have been alleviated, since doses required for enhancement in a number of brain regions appear to be safe for mice from neonatal stage to adulthood with no apparent abnormal behavior, at least over several months [28;29].…”

Section: Manganese-enhanced Magnetic Resonance Imagingmentioning

confidence: 99%

“…Initial concerns about neurotoxic effects of manganese have been alleviated, since doses required for enhancement in a number of brain regions appear to be safe for mice from neonatal stage to adulthood with no apparent abnormal behavior, at least over several months [28;29]. We have recently reported that this approach allows monitoring of deterioration of neuronal transport in mice as tau pathology advances with age [29], as well as in vivo detection of the beneficial effects of tau immunotherapy on neuronal transport in the same tauopathy mouse model [30]. …”

Section: Manganese-enhanced Magnetic Resonance Imagingmentioning

confidence: 99%

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Tau Immunotherapy and Imaging

Sigurdsson

2013

Neurodegener Dis

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Disappointing findings from recent phase III trials on amyloid-β (Aβ) immunotherapy for Alzheimer's disease (AD) have shifted the focus of such treatments to the tau protein. As tau pathology correlates better with the degree of dementia than Aβ plaque burden, it is a more attractive target once cognitive impairments are evident, while Aβ therapies may be better suited for the presymptomatic phase of the disease. Over 12 years ago, we initiated a tau immunotherapy program, seeking to alleviate the functional impairments associated with tau lesions in tauopathies. We have reported that various active and passive tau immunizations diminish tau pathology and improve function, including cognition, in different mouse models. Both extra- and intracellular pathways are likely involved. The antibodies may block the spread of tau pathology via microglial phagocytosis of the antibody-tau complex and facilitate lysosomal tau clearance in neurons after endosomal uptake. We have observed such antibody internalization following intracarotid injection in mice and in various culture models. These include brain slices and primary neurons from tangle mice as well as human neuroblastoma cell lines. Antibody targeting of different intracellular protein aggregates, including α-synuclein, Aβ and superoxide dismutase has been reported by others. Now, several laboratories have confirmed and extended our findings using various active and passive tau immunizations in different models, thereby clearly establishing the feasibility of this approach for clinical trials. We are also working on imaging approaches to monitor tau pathology, its consequences and the efficacy of treatments. Dire need exists for such diagnostic methods for tauopathies. Overall, therapies and diagnostic tools targeting tau pathology have a great potential for AD and other tauopathies.

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Section: Manganese-enhanced Magnetic Resonance Imagingmentioning

confidence: 99%

Section: Manganese-enhanced Magnetic Resonance Imagingmentioning

confidence: 99%

Tau Immunotherapy and Imaging

Sigurdsson

2013

Neurodegener Dis

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Tribute to Anne Bertrand (1978–2018): Neuroradiologist, scientist, teacher and friend

Dormont

Ben‐Eliezer

Burgos

et al. 2019

Journal of Neuroradiology

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Anne Bertrand passed away on March 2nd 2018. She was in a touring-skiers group led by a guide and swept by an avalanche in the French Alps. This paper is a tribute to Anne and an attempt, by some of her closest colleagues, to provide an overview of her major contributions. Anne Bertrand was a rising star of the neuroimaging community who traced innovative paths at the interface of basic science and clinical neuroradiology. From the very beginning of her career, she had been interested in the cross-fertilization between research and medical practice. After an MD and a specialization in neuroradiology, she prepared a PhD in preclinical imaging at the French Atomic Energy Commission (CEA) and at New York University. She was then appointed as Senior Neuroradiologist (at the Pitié-Salpêtrière and then Saint-Antoine Hospital in Paris) and Associate Professor (Sorbonne University). Simultaneously, she continued to develop her research activities in the ARAMIS Laboratory at the Brain and Spinal Cord Institute (ICM). Her main field of interest was neuroimaging of dementias. In a short time, she made important and exceptionally diverse contributions to the understanding, detection, diagnosis and tracking of these disorders (including Alzheimer's disease and fronto-temporal lobar degeneration) using advanced multimodal neuroimaging techniques. They will be a source of inspiration for all of us. Anne was not only an outstandingly bright scientist but also enlightening by her personal qualities: joy, openness, kindness and generosity.

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IC‐P‐064: Tau immunotherapy improves axonal transport as detected in vivo by manganese‐enhanced magnetic resonance imaging

Cited by 2 publications

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Tau Immunotherapy and Imaging

Tau Immunotherapy and Imaging

Tribute to Anne Bertrand (1978–2018): Neuroradiologist, scientist, teacher and friend

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