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

doi:10.1002/ana.24125

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

Global Public Health

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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. Ann Neurol 2014;75:597-601

Original language	English (US)
Pages (from-to)	597-601
Number of pages	5
Journal	Annals of Neurology
Volume	75
Issue number	4
DOIs	https://doi.org/10.1002/ana.24125
State	Published - Apr 2014

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1002/ana.24125

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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. Ann Neurol 2014;75:597-601",

author = "Alberto Serrano-Pozo and Jing Qian and Monsell, {Sarah E.} and Deborah Blacker and Teresa G{\'o}mez-Isla and Betensky, {Rebecca A.} and Growdon, {John H.} and Johnson, {Keith A.} and Frosch, {Matthew P.} and Sperling, {Reisa A.} and Hyman, {Bradley T.}",

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AU - Serrano-Pozo, Alberto

AU - Qian, Jing

AU - Monsell, Sarah E.

AU - Blacker, Deborah

AU - Gómez-Isla, Teresa

AU - Betensky, Rebecca A.

AU - Growdon, John H.

AU - Johnson, Keith A.

AU - Frosch, Matthew P.

AU - Sperling, Reisa A.

AU - Hyman, Bradley T.

PY - 2014/4

Y1 - 2014/4

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AB - 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

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Mild to moderate Alzheimer dementia with insufficient neuropathological changes

Abstract

ASJC Scopus subject areas

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