Journal
NATURE REVIEWS NEUROLOGY
Volume 12, Issue 2, Pages 117-124Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nrneurol.2015.251
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Funding
- NIH [P50-AG016574, P50-NS072187, P01-AG003949]
- Alexander Family Alzheimer disease Disease Research Professorship of the Mayo Foundation
- CurePSP: Foundation
- DIAN Pharma Consortium
- Alzheimer disease Association
- BrightFocus Foundation
- Netherlands Organization for Scientific Research (NWO)
- ZonMw
- Cardiovasculair Onderzoek Nederland
- European Union (EU) 7 Framework Programme
- EU Joint Programme-Neurodegenerative Disease Research (JPND)
- EU FP7
- Innovative Medicines Initiative joint resources
- Innovative Medicines Initiative Joint Undertaking under EMIF grant [115372]
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Suspected non-Alzheimer disease pathophysiology (SNAP) is a biomarker-based concept that applies to individuals with normal levels of amyloid-beta biomarkers in the brain, but in whom biomarkers of neurodegeneration are abnormal. The term SNAP has been applied to clinically normal individuals (who do not meet criteria for either mild cognitive impairment or dementia) and to individuals with mild cognitive impairment, but is applicable to any amyloid-negative, neurodegeneration-positive individual regardless of clinical status, except when the pathology underlying neurodegeneration can be reliably inferred from the clinical presentation. SNAP is present in similar to 23% of clinically normal individuals aged >65 years and in similar to 25% of mildly cognitively impaired individuals. APOE*epsilon 4 is underrepresented in individuals with SNAP compared with amyloid-positive individuals. Clinically normal and mildly impaired individuals with SNAP have worse clinical and/or cognitive outcomes than individuals with normal levels of neurodegeneration and amyloid-beta biomarkers. In this Perspectives article, we describe the available data on SNAP and address topical controversies in the field.
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