Journal
NEUROPATHOLOGY
Volume 35, Issue 4, Pages 390-400Publisher
WILEY
DOI: 10.1111/neup.12205
Keywords
autosomal dominant Alzheimer disease; late-onset Alzheimer disease; neuropathologic diagnostic criteria; neuropathologic heat map; PET-PiB amyloid imaging
Categories
Funding
- National Institute on Aging [P50 AG05681, P01 AG03991, P01 AG26276]
- DIAN from the National Institute on Aging [U01 AG032438]
- National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD [P30-NS048056]
- Charles and Joanne Knight Alzheimer's Research Initiative of the Washington University Alzheimer's Disease Research Center
- National Institute on Aging, the National Institute of Bio-medical Imaging and Bioengineering [U01 AG024904]
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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.
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