Positron Emission Tomography/Computed Tomography Imaging in Therapeutic Clinical Trials in Alzheimer’s Disease: An Overview of the Current State of the Art of Research

Issue title: Therapeutic Trials in Alzheimer’s Disease: Where Are We Now?

Guest editors: Paula I. Moreira, Jesus Avila, Daniela Galimberti, Miguel A. Pappolla, Germán Plascencia-Villa, Aaron A. Sorensen, Xiongwei Zhu and George Perry

Article type: Review Article

Authors: Triumbari, Elizabeth Katherine Anna^{a; 1} | Chiaravalloti, Agostino^{a; b; 1} | Schillaci, Orazio^a | Mercuri, Nicola Biagio^{c; d} | Liguori, Claudio^{c; d; *}

Affiliations: [a] Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy | [b] IRCCS Neuromed, Pozzilli, Italy | [c] Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy | [d] Neurology Unit, University Hospital of Rome “Tor Vergata”, Rome, Italy

Correspondence: [*] Correspondence to: Claudio Liguori, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1 – 00133, Rome, Italy. Tel.: +390620903132; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: The integration of positron emission tomography/computed tomography (PET/CT) has revolutionized the landscape of Alzheimer’s disease (AD) research and therapeutic interventions. By combining structural and functional imaging, PET/CT provides a comprehensive understanding of disease pathology and response to treatment assessment. PET/CT, particularly with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG), facilitates the visualization of glucose metabolism in the brain, enabling early diagnosis, staging, and monitoring of neurodegenerative disease progression. The advent of amyloid and tau PET imaging has further propelled the field forward, offering invaluable tools for tracking pathological hallmarks, assessing treatment response, and predicting clinical outcomes. While some therapeutic interventions targeting amyloid plaque load showed promising results with the reduction of cerebral amyloid accumulation over time, others failed to demonstrate a significant impact of anti-amyloid agents for reducing the amyloid plaques burden in AD brains. Tau PET imaging has conversely fueled the advent of disease-modifying therapeutic strategies in AD by supporting the assessment of neurofibrillary tangles of tau pathology deposition over time. Looking ahead, PET imaging holds immense promise for studying additional targets such as neuroinflammation, cholinergic deficit, and synaptic dysfunction. Advances in radiotracer development, dedicated brain PET/CT scanners, and Artificial Intelligence-powered software are poised to enhance the quality, sensitivity, and diagnostic power of molecular neuroimaging. Consequently, PET/CT remains at the forefront of AD research, offering unparalleled opportunities for unravelling the complexities of the disease and advancing therapeutic interventions, although it is not yet enough alone to allow patients’ recruitment in therapeutic clinical trials.

Keywords: Alzheimer’s disease, amyloid, cerebrospinal fluid, disease-modifying treatment, FDG, PET/CT, tau, trial

DOI: 10.3233/JAD-240349

Journal: Journal of Alzheimer's Disease, vol. 101, no. s1, pp. S603-S628, 2024