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Updated: May 2, 2026

Symmetric Bihemispheric Postmortem Brain Cutting to Study Healthy and Pathological Brain Conditions in Humans
Published on: December 18, 2016
Mild to moderate Alzheimer dementia with insufficient neuropathological changes
Alberto Serrano-Pozo1, Jing Qian, Sarah E Monsell
1Massachusetts 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.
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.
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