TY - JOUR
T1 - Cross-sectional and longitudinal comparisons of biomarkers and cognition among asymptomatic middle-aged individuals with a parental history of either autosomal dominant or late-onset Alzheimer's disease
AU - and Dominantly Inherited Alzheimer Network (DIAN)
AU - Xiong, Chengjie
AU - McCue, Lena M.
AU - Buckles, Virginia
AU - Grant, Elizabeth
AU - Agboola, Folasade
AU - Coble, Dean
AU - Bateman, Randall J.
AU - Fagan, Anne M.
AU - Benzinger, Tammie L.S.
AU - Hassenstab, Jason
AU - Schindler, Suzanne E.
AU - McDade, Eric
AU - Moulder, Krista
AU - Gordon, Brian A.
AU - Cruchaga, Carlos
AU - Day, Gregory S.
AU - Ikeuchi, Takeshi
AU - Suzuki, Kazushi
AU - Allegri, Ricardo F.
AU - Vöglein, Jonathan
AU - Levin, Johannes
AU - Morris, John C.
N1 - Funding Information:
This study was supported by National Institute on Aging (NIA) grants R01 AG053550 (Dr Xiong), P01 AG026276 (Dr Morris), and UF1AG032438 (Dr Bateman), as well as the German Center for Neurodegenerative Diseases (DZNE), the Raul Carrea Institute for Neurological Research (FLENI), Japan Agency for Medical Research and Development (AMED) grants for DIAN‐J (PI Hiroshi Mori, PhD)), and the generous support of Fred Simmons and Olga Mohan. The authors thank the Genetics Core (Alison Goate and Carlos Cruchaga, Core Leaders) of the Knight Alzheimer Disease Research Center (ADRC; P50 AG05681) and the DIAN for the genetic data. The corresponding author (C Xiong) had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Funding Information:
Drs. Xiong, Schindler, Fagan, Benzinger, Hassenstab, Balls‐Berry, Moulder, and Morris all have received research funding from the National Institute on Aging of the National Institutes of Health that was made to their institutions. Dr. Hassenstab also has received BrightFocus grant that was made to his institution. Dr. Morris received royalties or licenses for CDR registration, and received support for attending meetings and/or travel (Srinivasan 40th Oration, India; World Congress of Neurology; Cure Alzheimer's Board meeting; CBR Intl' Advisory Board). Dr. Xiong consults for Diadem. Dr. Schindler consults for National Institute on Aging Alzheimer Disease Center Clinical (ADC) Task Force, to me National Centralized Repository for Alzheimer Disease. Dr. Fagan has received research funding from the National Institute on Aging of the National Institutes of Health, Biogen, Centene, Fujirebio and Roche Diagnostics. She is a member of the scientific advisory boards for Roche Diagnostics, Genentech and AbbVie and also consults for Diadem, DiamiR and Otsuka Pharmaceuticals. Dr. Fagan also consults for Seimens Healthcare Diagnostics. Dr. Benzinger consults for Biogen. Dr. Hassenstab consults for Lundbeck, Eisai, Roch, and Parabon Labs. Dr. Morris consults for Barcelona Betabrain Research Center, BBRC SAB meeting, Barcelona Centre for Brain Research meeting, Bangalore, India. Dr. Schindler received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from University of Wisconsin and St. Luke's Hospital. Dr. Benzinger received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Biogen. Dr. Hassenstab received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events: (seminar speaker) from Alzheimer's Therapeutic Research Institute (ATRI), University of Southern California. Dr. Morris received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events: (Grand Rounds lecture) from Montefiore, NY. Drs. Xiong, Benzinger, Hassenstab, and Balls‐Berry all served on Data Safety Monitoring Board or Advisory Board for FDA or NIH‐funded studies. Dr. Schindler is a Member of the Board of Directors, Alzheimer's Association Greater Missouri Chapter. Dr. Balls‐Berry is President of the Board of Directors for Health Literacy Media. Dr. Morris is a member of Cure Alzheimer's Board. Avid Radiopharmacueticals and Life Molecular Imaging have provided reagents and technology transfer agreements to Dr. Benzinger's institution for the production of radiopharmaceuticals. TI is supported by Japan Agency for Medical Research and Development (AMED) JP21dk0207049. There are no conflicts with this work. GSD is supported by National Institutes of Health /National Institute on Aging (K23AG064029). He serves as a topic editor on dementia for DynaMed Plus (EBSCO Industries, Inc), a consultant for Parabon NanoLabs, is the clinical director for the Anti‐NMDA Receptor Encephalitis Foundation (uncompensated), has provided record review and expert medical testimony on legal cases pertaining to management of Wernicke encephalopathy, and holds stocks (>$10,000) in ANI Pharmaceuticals (a generic pharmaceutical company). There are no conflicts with this work. Johannes Levin reports speaker fees from Bayer Vital, Biogen and Roche, consulting fees from Axon Neuroscience, author fees from Thieme medical publishers and W. Kohlhammer GmbH medical publishers, non‐financial support from Abbvie and compensation for duty as part‐time CMO from MODAG, outside the submitted work.
Publisher Copyright:
© 2023 the Alzheimer's Association.
PY - 2023/7
Y1 - 2023/7
N2 - Background: Comparisons of late-onset Alzheimer's disease (LOAD) and autosomal dominant AD (ADAD) are confounded by age. Methods: We compared biomarkers from cerebrospinal fluid (CSF), magnetic resonance imaging, and amyloid imaging with Pittsburgh Compound-B (PiB) across four groups of 387 cognitively normal participants, 42 to 65 years of age, in the Dominantly Inherited Alzheimer Network (DIAN) and the Adult Children Study (ACS) of LOAD: DIAN mutation carriers (MCs) and non-carriers (NON-MCs), and ACS participants with a positive (FH+) and negative (FH–) family history of LOAD. Results: At baseline, MCs had the lowest age-adjusted level of CSF Aβ42 and the highest levels of total and phosphorylated tau-181, and PiB uptake. Longitudinally, MC had similar increase in PiB uptake to FH+, but drastically faster decline in hippocampal volume than others, and was the only group showing cognitive decline. Discussion: Preclinical ADAD and LOAD share many biomarker signatures, but cross-sectional and longitudinal differences may exist.
AB - Background: Comparisons of late-onset Alzheimer's disease (LOAD) and autosomal dominant AD (ADAD) are confounded by age. Methods: We compared biomarkers from cerebrospinal fluid (CSF), magnetic resonance imaging, and amyloid imaging with Pittsburgh Compound-B (PiB) across four groups of 387 cognitively normal participants, 42 to 65 years of age, in the Dominantly Inherited Alzheimer Network (DIAN) and the Adult Children Study (ACS) of LOAD: DIAN mutation carriers (MCs) and non-carriers (NON-MCs), and ACS participants with a positive (FH+) and negative (FH–) family history of LOAD. Results: At baseline, MCs had the lowest age-adjusted level of CSF Aβ42 and the highest levels of total and phosphorylated tau-181, and PiB uptake. Longitudinally, MC had similar increase in PiB uptake to FH+, but drastically faster decline in hippocampal volume than others, and was the only group showing cognitive decline. Discussion: Preclinical ADAD and LOAD share many biomarker signatures, but cross-sectional and longitudinal differences may exist.
KW - Alzheimer's disease (AD)
KW - Pittsburgh compound-B (PiB)
KW - autosomal dominant Alzheimer's disease (ADAD), cerebrospinal fluid (CSF)
KW - magnetic resonance imaging (MRI)
KW - positron emission tomography (PET)
UR - http://www.scopus.com/inward/record.url?scp=85146308723&partnerID=8YFLogxK
U2 - 10.1002/alz.12912
DO - 10.1002/alz.12912
M3 - Article
C2 - 36640138
AN - SCOPUS:85146308723
SN - 1552-5260
VL - 19
SP - 2923
EP - 2932
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 7
ER -