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Mild to moderate Alzheimer dementia with insufficient neuropathological changes
Open accessAbstract
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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“Thus, the multidomain amnestic dementia phenotype is not specific; it can be the product of other diseases as well as AD [51].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [51]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“AD neuropathologic change is documented in approximately 80% of cases with a traditional clinical diagnosis of “AD dementia” (see Fig. 5 for an example of clinical misdiagnosis of “AD dementia”) [50–52,162,185,209–211].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [51]
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“It is now well established that the prototypical multidomain amnestic dementia phenotype historically used to define probable AD [1] does not “rule in” AD pathologic change (which implies change from normal) at autopsy [50–52]”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [51]
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“and the absence of the syndrome does not “rule out” AD pathologic change.”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [51]
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Metadata
- Authors
- 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.
- Affiliations
- University of Iowa Hospitals and Clinics (US)
- University of Massachusetts Amherst (US)
- University of Washington (US)
- Harvard University (US)
- Massachusetts General Hospital (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Hyman, Bradley T.
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2014-04
- Volume
- 75
- Issue
- 4
- Pages
- 597-601
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC4016558
- OpenAlex
- W2171032841
- Cited by
- 120
- References
- 23
- Citations by year
- 2026: 3 · 2025: 15 · 2024: 10 · 2023: 10 · 2022: 14 · 2021: 9 · 2020: 11 · 2019: 9 · 2018: 6 · 2017: 9 · 2016: 11 · 2015: 10 · 2014: 3
- FWCI
- 8.40
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (P50 AG0001534, U01AG016976, P50AG005134, P30AG062421)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid PET, neuritic plaques, neurofibrillary tangles, Braak stages, neuropathology, trial inclusion criteria
- MeSH terms
- Aged, Aged, 80 and over, Algorithms, Alzheimer Disease, Apolipoproteins E, Autopsy, Brain, Female, Humans, Male, Mental Status Schedule, Middle Aged, Retrospective Studies, Cohort Studies, Disease Progression
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