title: Mild to moderate Alzheimer dementia with insufficient neuropathological changes.
abstract: Recently, ~16% of participants in an anti-Aβ passive immunotherapy trial for mild-to-moderate Alzheimer disease (AD) had a negative baseline amyloid positron emission tomography (PET) scan. Whether they have AD or are AD clinical phenocopies remains unknown. We examined the 2005-2013 National Alzheimer's Coordinating Center autopsy database and found that ~14% of autopsied subjects clinically diagnosed with mild-to-moderate probable AD have no or sparse neuritic plaques, which would expectedly yield a negative amyloid PET scan. More than half of these "Aβ-negative" subjects have low neurofibrillary tangle Braak stages. These findings support the implementation of a positive amyloid biomarker as an inclusion criterion in future anti-Aβ drug trials.
authors.affiliation: Massachusetts Alzheimer Disease Research Center, Charlestown, MA; Department of Neurology, Massachusetts General Hospital, Boston, MA; Department of Neurology, University of Iowa Hospitals & Clinics, Iowa city, IA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Serrano-Pozo
authors.forename: Jing
authors.initials: J
authors.lastname: Qian
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Monsell
authors.forename: Deborah
authors.initials: D
authors.lastname: Blacker
authors.forename: Teresa
authors.initials: T
authors.lastname: Gómez-Isla
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Betensky
authors.forename: John H
authors.initials: JH
authors.lastname: Growdon
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Frosch
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics; D001344:Autopsy; D001921:Brain / Q000473:pathology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D001057:Apolipoproteins E