title: Suspected non-Alzheimer disease pathophysiology--concept and controversy.
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*ε4 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.
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: INSERM, Université de Caen, EPHE, CHU de Caen, U1077, Caen, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Chételat
authors.affiliation: Department of Pathology, Mayo Clinic and Foundation, 4500 San Pablo Road South, Jacksonville, Florida 32224, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Dickson
authors.affiliation: Department of Neurology, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, 4488 Forest Park Avenue, Suite 101, St Louis, Missouri 63108, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
authors.affiliation: University Hospitals and University of Geneva, Rue Gabrielle-Perret-Gentil 4, 1205 Genève, Switzerland.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
authors.affiliation: Helen Wills Neuroscience Institute, University of California Berkeley, 175 Li Ka Shing Center, Berkeley, California 94720, USA.
authors.forename: William
authors.initials: W
authors.lastname: Jagust
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Mormino
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.affiliation: Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, PO Box 7057, 1007 MB Amsterdam, Netherlands.
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.affiliation: Department of Molecular Imaging &Therapy, Centre for PET, Austin Health, 145 Studley Road, PO Box 5555 Melbourne, Victoria, Australia 3084.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.affiliation: Department of Psychiatry and Neuropsychology, Institute of Mental Health and Neuroscience, Maastricht University, PO Box 616 MD Maastricht, Netherlands.
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Visser
authors.affiliation: Department of Psychiatry and Neuropsychology, Institute of Mental Health and Neuroscience, Maastricht University, PO Box 616 MD Maastricht, Netherlands.
authors.forename: Stephanie J B
authors.initials: SJ
authors.lastname: Vos
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology / Q000523:psychology; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000473:pathology* / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D006801:Humans
chemical_list: D015415:Biomarkers