title: Neuropathologic assessment of participants in two multi-center longitudinal observational studies: the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN).
abstract: It has been hypothesized that the relatively rare autosomal dominant Alzheimer disease (ADAD) may be a useful model of the more frequent, sporadic, late-onset AD (LOAD). Individuals with ADAD have a predictable age at onset and the biomarker profile of ADAD participants in the preclinical stage may be used to predict disease progression and clinical onset. However, the extent to which the pathogenesis and neuropathology of ADAD overlaps with that of LOAD is equivocal. To address this uncertainty, two multicenter longitudinal observational studies, the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN), leveraged the expertise and resources of the existing Knight Alzheimer Disease Research Center (ADRC) at Washington University School of Medicine, St. Louis, Missouri, USA, to establish a Neuropathology Core (NPC). The ADNI/DIAN-NPC is systematically examining the brains of all participants who come to autopsy at the 59 ADNI sites in the USA and Canada and the 14 DIAN sites in the USA (eight), Australia (three), UK (one) and Germany (two). By 2014, 41 ADNI and 24 DIAN autopsies (involving nine participants and 15 family members) had been performed. The autopsy rate in the ADNI cohort in the most recent year was 93% (total since NPC inception: 70%). In summary, the ADNI/DIAN NPC has implemented a standard protocol for all sites to solicit permission for brain autopsy and to send brain tissue to the NPC for a standardized, uniform and state-of-the-art neuropathologic assessment. The benefit to ADNI and DIAN of the implementation of the NPC is very clear. The NPC provides final "gold standard" neuropathological diagnoses and data against which the antecedent observations and measurements of ADNI and DIAN can be compared.
authors.affiliation: Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.|Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.|Division of Neuropathology, Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.affiliation: Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.|Division of Neuropathology, Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Perrin
authors.affiliation: Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.|Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Franklin
authors.affiliation: Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.|Division of Neuropathology, Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Carter
authors.affiliation: Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.|Division of Neuropathology, Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Vincent
authors.affiliation: Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.|Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Xie
authors.affiliation: Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.|Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Bateman
authors.affiliation: Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.|Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Tammie
authors.initials: T
authors.lastname: Benzinger
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Friedrichsen
authors.affiliation: Neuroscience Research Australia, Sydney, New South Wales, Australia.|Department of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: William S
authors.initials: WS
authors.lastname: Brooks
authors.affiliation: Neuroscience Research Australia, Sydney, New South Wales, Australia.|Department of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria, Australia.
authors.forename: Catriona
authors.initials: C
authors.lastname: McLean
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.affiliation: Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.|Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.|Division of Neuropathology, Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D001344:Autopsy / Q000706:statistics & numerical data; D015415:Biomarkers; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D059906:Neuroimaging; D009926:Organ Preservation; D014015:Tissue Banks
chemical_list: D015415:Biomarkers
keywords: PET-PiB amyloid imaging; autosomal dominant Alzheimer disease; late-onset Alzheimer disease; neuropathologic diagnostic criteria; neuropathologic heat map