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. 2021 Dec;17(12):2043-2055.
doi: 10.1002/alz.12350. Epub 2021 May 21.

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

Liana G Apostolova  1   2   3 , Paul Aisen  4 , Ani Eloyan  5 , Anne Fagan  6 , Keith N Fargo  7 , Tatiana Foroud  3 , Constantine Gatsonis  5 , Lea T Grinberg  8   9 , Clifford R Jack Jr  10 , Joel Kramer  9 , Robert Koeppe  11 , Walter A Kukull  12 , Melissa E Murray  13 , Kelly Nudelman  3 , Malia Rumbaugh  3 , Arthur Toga  14 , Prashanthi Vemuri  10 , Amy Trullinger  15 , Leonardo Iaccarino  9 , Gregory S Day  16 , Neill R Graff-Radford  16 , Lawrence S Honig  17 , David T Jones  10   18 , Joseph Masdeu  19 , Mario Mendez  20 , Erik Musiek  6 , Chiadi U Onyike  21 , Emily Rogalski  22 , Steve Salloway  23 , David A Wolk  24 , Thomas S Wingo  25 , Maria C Carrillo  26 , Bradford C Dickerson  27 , Gil D Rabinovici  9 ; LEADS Consortium  1
Affiliations

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

Liana G Apostolova et al. Alzheimers Dement. 2021 Dec.

Abstract

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), [18 F]Florbetaben and [18 F]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.

Keywords: Alzheimer's disease; EOAD; LEADS; YOAD; early-onset; young onset.

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Conflict of interest statement

Dr. Apostolova served as a paid consultant for Biogen and Two Labs, serves on a DSMB for IQVIA, and receives research support from the NIH, the Alzheimer's Association, Roche, Life Molecular Imaging, and Eli Lilly. Dr. Aisen reports grants from NIA, FNIH, the Alzheimer's Association, Janssen, Lilly, and Eisai, and personal fees from Merck, Roche, Biogen, Lundbeck, ImmunoBrain Checkpoint, and Samus. Dr. Eloyan has nothing to disclose. Dr. Fagan has received research support from Biogen, Fujirebio, and Roche Diagnostics. She is a member of the scientific advisory boards for Roche Diagnostics, Genentech, and AbbVie and also consults for Araclon/Griffols, DiademRes, and Otsuka Pharmaceuticals. Dr. Fargo has nothing to disclose. Dr. Foroud has nothing to disclose. Dr. Gatsonis has nothing to disclose. Dr. Grinberg has nothing to disclose. Dr. Jack serves on an independent data monitoring board for Roche and has consulted for and served as a speaker for Eisai, but he receives no personal compensation from any commercial entity. He receives research support from the NIH and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic. Dr. Kramer has nothing to disclose. Dr. Koeppe has nothing to disclose. Dr. Kukull is supported by the NIA. Dr. Murray served as a paid consultant for AVID Radiopharmaceuticals and receives research support from the NIH, the Alzheimer's Association, and the state of Florida. Dr. Nudelman has nothing to disclose. Mrs. Rumbaugh has nothing to disclose. Dr. Toga has nothing to disclose. Dr. Vemuri has nothing to disclose. Mrs. Trullinger has nothing to disclose. Dr. Iaccarino has nothing to disclose. Dr. Day is supported by the NIA; he serves as a topic editor on dementia for DynaMed Plus (EBSCO Industries, Inc), is the clinical director for the Anti‐NMDA Receptor Encephalitis Foundation and holds stocks in ANI Pharmaceuticals. Dr. Graff‐Radford receives research support from Lilly, AbbVie, and Biogen. Dr. Honig has nothing to disclose. Dr. Jones has nothing to disclose. Dr. Masdeu served on the speaker's bureau and consulted for Biogen. He received research support from the NIH, Avanir, Abbvie, Biogen, Eli Lilly, Esai, and Novartis. Dr. Mendez receives grant support from NIA and has received support from Biogen. Dr. Musiek received research funding from Eisai Pharmaceuticals Inc. Dr. Onyike has nothing to disclose. Dr. Rogalski has nothing to disclose. Dr. Salloway received consultation fees and research support from Biogen, Eisai, Lilly, Genentech, and Roche. Dr. Wolk received grants from Eli Lilly/Avid Radiopharmaceuticals, Merck, and Biogen, and consulted for Merck, Janssen, and GE Healthcare. Dr. Wingo has nothing to disclose. Dr. Carrillo has nothing to disclose. Dr. Dickerson receives research support from the NIH and the Alzheimer's Drug Discovery Foundation. He consulted for Arkuda, Axovant, Lilly, Biogen, Merck, Novartis, and Wave LifeSciences. He is editor for Neuroimage: Clinical and Cortex. He receives royalties from Oxford University Press and Cambridge University Press. Dr. Rabinovici receives research support from the NIH, Alzheimer's Association, American College of Radiology, Rainwater Charitable Foundation, Avid Radiopharmaceuticals, Eli Lilly, GE Healthcare, Life Molecular Imaging, Genentech, and Roche. He has served as a paid consultant for Axon Neurosciences, Eisai, GE Healthcare, Genentech, Roche, and Johnson & Johnson, and is an Associate Editor for JAMA Neurology.

Figures

FIGURE 1
FIGURE 1
Schedule of events
FIGURE 2
FIGURE 2
PET data processing
FIGURE 3
FIGURE 3
LEADS data flow
See this image and copyright information in PMC

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