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The Longitudinal Early‐onset Alzheimer's Disease Study (LEADS): Framework and methodology

Perspective
Liana G Apostolova, Paul Aisen, Ani Eloyan, Anne Fagan, Keith N Fargo, Tatiana Foroud, Constantine Gatsonis, Lea T Grinberg, Clifford R Jack Jr, Joel Kramer, Robert Koeppe, Walter A Kukull, Melissa E Murray, Kelly Nudelman, Malia Rumbaugh, Arthur Toga, Prashanthi Vemuri, Amy Trullinger, Leonardo Iaccarino, Gregory S Day, Neill R Graff‐Radford, Lawrence S Honig, David T Jones, Joseph Masdeu, Mario Mendez, Erik Musiek, Chiadi U Onyike, Emily Rogalski, Steve Salloway, David A Wolk, Thomas S Wingo, Maria C Carrillo, Bradford C Dickerson, Gil D Rabinovici, LEADS Consortium
Alzheimer's & Dementia. Online-Only
Publication year: 2021

Patients with early-onset Alzheimer’s disease (EOAD) are commonly excluded from large-scale observational and therapeutic studies due to their young age, atypical presentation, or absence of pathogenic mutations. The goals of the Longitudinal EOAD Study (LEADS) are to (1) define the clinical, imaging, and fluid biomarker characteristics of EOAD; (2) develop sensitive cognitive and biomarker measures for future clinical and research use; and (3) establish a trial-ready network. LEADS will follow 400 amyloid beta (Aβ)-positive EOAD, 200 Aβ-negative EOnonAD that meet National Institute on Aging–Alzheimer’s Association (NIA-AA) criteria for mild cognitive impairment (MCI) or AD dementia, and 100 age-matched controls. Participants will undergo clinical and cognitive assessments, magnetic resonance imaging (MRI), [18F]Florbetaben and [18F]Flortaucipir positron emission tomography (PET), lumbar puncture, and blood draw for DNA, RNA, plasma, serum and peripheral blood mononuclear cells, and post-mortem assessment. To develop more effective AD treatments, scientists need to understand the genetic, biological, and clinical processes involved in EOAD. LEADS will develop a public resource that will enable future planning and implementation of EOAD clinical trials.

A new perspective for advanced positron emission tomography–based molecular imaging in neurodegenerative proteinopathies

Perspective
Daniela Perani, Leonardo Iaccarino, Adriaan A Lammertsma, Albert D Windhorst, Paul Edison, Ronald Boellaard, Oskar Hansson, Agneta Nordberg, Andreas H Jacobs, Michel Bottlaender, David Brooks, Michael A Carroll, Sylvie Chalon, Anthony Gee, Alexander Gerhard, Christer Halldin, Karl Herholz, Matthias M Herth, Rainer Hinz, Gitte M Knudsen, Bertrand Kuhnast, Francisco López-Picón, Rosa Maria Moresco, Sabina Pappata, Juha O Rinne, Elena Rodriguez-Vieitez, Marie Joao Santiago-Ribeiro, Federico E Turkheimer, Koen Van Laere, Andrea Varrone, Johnny Vercouillie, Alexandra Winkeler
Alzheimer's & Dementia Volume 15, Issue 8, August 2019, Pages 1081-1103
Publication year: 2019

Recent studies in neurodegenerative conditions have increasingly highlighted that the same neuropathology can trigger different clinical phenotypes or, vice-versa, that similar phenotypes can be triggered by different neuropathologies. This evidence has called for the adoption of a pathology spectrum-based approach to study neurodegenerative proteinopathies. These conditions share brain deposition of abnormal protein aggregates, leading to aberrant biochemical, metabolic, functional, and structural changes. Positron emission tomography (PET) is a well-recognized and unique tool for the in vivo assessment of brain neuropathology, and novel PET techniques are emerging for the study of specific protein species. Today, key applications of PET range from early research and clinical diagnostic tools to their use in clinical trials for both participants screening and outcome evaluation. This position article critically reviews the role of distinct PET molecular tracers for different neurodegenerative proteinopathies, highlighting their strengths, weaknesses, and opportunities, with special emphasis on methodological challenges and future applications.