Suspected non-Alzheimer disease pathophysiology-concept and controversy

Clifford R. Jack, David S. Knopman, Gaël Chételat, Dennis Dickson, Anne M. Fagan, Giovanni B. Frisoni, William Jagust, Elizabeth C. Mormino, Ronald C. Petersen, Reisa A. Sperling, Wiesje M. Van Der Flier, Victor L. Villemagne, Pieter J. Visser, Stephanie J.B. Vos

Research output: Contribution to journalReview article

139 Scopus citations

Abstract

Suspected non-Alzheimer disease pathophysiology (SNAP) is a biomarker-based concept that applies to individuals with normal levels of amyloid-β 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 ∼23% of clinically normal individuals aged >65 years and in ∼25% of mildly cognitively impaired individuals. APOE∗ε 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-β biomarkers. In this Perspectives article, we describe the available data on SNAP and address topical controversies in the field.

Original languageEnglish
Pages (from-to)117-124
Number of pages8
JournalNature Reviews Neurology
Volume12
Issue number2
DOIs
StatePublished - Feb 1 2016

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    Jack, C. R., Knopman, D. S., Chételat, G., Dickson, D., Fagan, A. M., Frisoni, G. B., Jagust, W., Mormino, E. C., Petersen, R. C., Sperling, R. A., Van Der Flier, W. M., Villemagne, V. L., Visser, P. J., & Vos, S. J. B. (2016). Suspected non-Alzheimer disease pathophysiology-concept and controversy. Nature Reviews Neurology, 12(2), 117-124. https://doi.org/10.1038/nrneurol.2015.251