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Application of advanced brain positron emission tomography–based molecular imaging for a biological framework in neurodegenerative proteinopathies

Review
Daniela Perani, Leonardo Iaccarino, Andreas H Jacobs, Adriaan A Lammertsma, Agneta Nordberg, Albert D Windhorst, Alexander Gerhard, Alexandra Winkeler, Anthony Gee, Bertrand Kuhnast, Christer Halldin, David Brooks, Elena Rodriguez-Vieitez, Federico E Turkheimer, Francisco López-Picón, Gitte M Knudsen, Johnny Vercouillie, Juha O Rinne, Karl Herholz, Koen Van Laere, Marie Joao Santiago-Ribeiro, Matthias M Herth, Michael A Carroll, Michel Bottlaender, Oskar Hansson, Paul Edison, Rainer Hinz, Ronald Boellaard, Rosa Maria Moresco, Sabina Pappatà
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, Volume 11, Pages 327-332
Publication year: 2019

Introduction

A rapid transition from a clinical-based classification to a pathology-based classification of neurodegenerative conditions, largely promoted by the increasing availability of imaging biomarkers, is emerging. The Framework for Innovative Multi-tracer molecular Brain Imaging, funded by the EU Joint Program – Neurodegenerative Disease Research 2016 “Working Groups for Harmonisation and Alignment in Brain Imaging Methods for Neurodegeneration,” aimed at providing a roadmap for the applications of established and new molecular imagingtechniques in dementia.

Methods

We consider current and future implications of adopting a pathology-based framework for the use and development of positron emission tomography techniques.

Results

This approach will enhance efforts to understand the multifactorial etiology of Alzheimer’s disease and other dementias.

Discussion

The availability of pathology biomarkers will soon transform clinical and research practice. Crucially, a comprehensive understanding of strengths and caveats of these techniques will promote an informed use to take full advantage of these tools.

The emerging role of PET imaging in dementia

Review
Iaccarino, L., Sala, A., Caminiti SP. & Perani D.
F1000Res. 2017 Oct 12;6:1830. doi: 10.12688/f1000research.11603.1
Publication year: 2017

A compelling need in the field of neurodegenerative diseases is the development and validation of biomarkers for early identification and differential diagnosis. The availability of positron emission tomography (PET) neuroimaging tools for the assessment of molecular biology and neuropathology has opened new venues in the diagnostic design and the conduction of new clinical trials. PET techniques, allowing the in vivo assessment of brain function and pathology changes, are increasingly showing great potential in supporting clinical diagnosis also in the early and even preclinical phases of dementia. This review will summarize the most recent evidence on fluorine-18 fluorodeoxyglucose-, amyloid -, tau -, and neuroinflammation – PET tools, highlighting strengths and limitations and possible new perspectives in research and clinical applications. Appropriate use of PET tools is crucial for a prompt diagnosis and target evaluation of new developed drugs aimed at slowing or preventing dementia.

Targeting neuroinflammation to treat Alzheimer's Disease

Review
A. Ardura-Fabregat, E. W. G. M. Boddeke, A. Boza-Serrano, S. Brioschi, S. Castro-Gomez, K. Ceyzériat, C. Dansokho, T. Dierkes, G. Gelders, Michael T. Heneka, L. Hoeijmakers, A. Hoffmann, L. Iaccarino, S. Jahnert, K. Kuhbandner, G. Landreth, N. Lonnemann, P. A. Löschmann, R. M. McManus, A. Paulus, K. Reemst, J. M. Sanchez-Caro, A. Tiberi, A. Van der Perren, A. Vautheny, C. Venegas, A. Webers, P. Weydt, T. S. Wijasa, X. Xiang, Y. Yang
CNS Drugs, 2017, online-first, https://doi.org/10.1007/s40263-017-0483-3
Publication year: 2017

Over the past few decades, research on Alzheimer’s disease (AD) has focused on pathomechanisms linked to two of the major pathological hallmarks of extracellular deposition of beta-amyloid peptides and intra-neuronal formation of neurofibrils. Recently, a third disease component, the neuroinflammatory reaction mediated by cerebral innate immune cells, has entered the spotlight, prompted by findings from genetic, pre-clinical, and clinical studies. Various proteins that arise during neurodegeneration, including beta-amyloid, tau, heat shock proteins, and chromogranin, among others, act as danger-associated molecular patterns, that—upon engagement of pattern recognition receptors—induce inflammatory signaling pathways and ultimately lead to the production and release of immune mediators. These may have beneficial effects but ultimately compromise neuronal function and cause cell death. The current review, assembled by participants of the Chiclana Summer School on Neuroinflammation 2016, provides an overview of our current understanding of AD-related immune processes. We describe the principal cellular and molecular players in inflammation as they pertain to AD, examine modifying factors, and discuss potential future therapeutic targets.

Molecular Imaging of Neuroinflammation in Neurodegenerative Dementias: The Role of In Vivo PET Imaging

Review
Cerami C., Iaccarino, L., Perani D.
Int. J. Mol. Sci. 2017, 18(5), 993; doi:10.3390/ijms18050993
Publication year: 2017

Neurodegeneration elicits neuroinflammatory responses to kill pathogens, clear debris and support tissue repair. Neuroinflammation is a dynamic biological response characterized by the recruitment of innate and adaptive immune system cells in the site of tissue damage. Resident microglia and infiltrating immune cells partake in the restoration of central nervous system homeostasis. Nevertheless, their activation may shift to chronic and aggressive responses, which jeopardize neuron survival and may contribute to the disease process itself. Positron Emission Tomography (PET) molecular imaging represents a unique tool contributing to in vivo investigating of neuroinflammatory processes in patients. In the present review, we first provide an overview on the molecular basis of neuroinflammation in neurodegenerative diseases with emphasis on microglia activation, astrocytosis and the molecular targets for PET imaging. Then, we review the state-of-the-art of in vivo PET imaging for neuroinflammation in dementia conditions associated with different proteinopathies, such as Alzheimer’s disease, frontotemporal lobar degeneration and Parkinsonian spectrum

Utilization Behavior: What is Known and what has to be known?

Review
Iaccarino, L., Chieffi, S., Iavarone, A
Behavioural Neurology, 2014, doi: 10.1155/2014/297128
Publication year: 2014

The need for “objective measurements” in Amyloid and FDG-PET neuroimaging

Review
Perani, D., Iaccarino, L., Bettinardi, V
Clinical and Translation Imaging, 2(4):331-342
Publication year: 2014

PET neuroimaging: insights on dystonia and Tourette syndrome and potential applications

Review
Alongi, P., Iaccarino, L. and Perani, D.
Frontiers in Neurology, 5, 2014.
Publication year: 2014