Mild to moderate Alzheimer dementia with insufficient neuropathological changes

Alberto Serrano-Pozo, Jing Qian, Sarah E. Monsell, Deborah Blacker, Teresa Gómez-Isla, Rebecca A. Betensky, John H. Growdon, Keith A. Johnson, Matthew P. Frosch, Reisa A. Sperling, Bradley T. Hyman

Research output: Contribution to journalArticle


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. Ann Neurol 2014;75:597-601

Original languageEnglish (US)
Pages (from-to)597-601
Number of pages5
JournalAnnals of Neurology
Issue number4
StatePublished - Apr 2014

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Serrano-Pozo, A., Qian, J., Monsell, S. E., Blacker, D., Gómez-Isla, T., Betensky, R. A., Growdon, J. H., Johnson, K. A., Frosch, M. P., Sperling, R. A., & Hyman, B. T. (2014). Mild to moderate Alzheimer dementia with insufficient neuropathological changes. Annals of Neurology, 75(4), 597-601.