The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123
Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961
Hyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.10.007 · Cited by 3,092
Self-citationConsortium to Establish a Registry for Alzheimer's Disease (CERAD)
Fillenbaum, G., & Heyman, A. (2002) · doi:10.1002/0470846410.ch42(iii · Cited by 2,859
Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease
Salloway, S., Sperling, R., Fox, N. C., Blennow, K., Klunk, W., Raskind, M., Sabbagh, M., Honig, L. S., Porsteinsson, A. P., Ferris, S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1304839 · Cited by 1,960
Self-citationHYMAN, B. T., & TROJANOWSKI, J. Q. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199710000-00002 · Cited by 1,542
Self-citationBeach, T. G., Monsell, S. E., Phillips, L. E., & Kukull, W. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31824b211b · Cited by 1,103
Self-citationConsensus Recommendations for the Postmortem Diagnosis of Alzheimer’s Disease
(1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00057-2 · Cited by 981
Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease
Ikonomovic, M. D., Klunk, W. E., Abrahamson, E. E., Mathis, C. A., Price, J. C., Tsopelas, N. D., Lopresti, B. J., Ziolko, S., Bi, W., Paljug, W. R., et al. (2008) · Brain · doi:10.1093/brain/awn016 · Cited by 933
The National Alzheimer's Coordinating Center (NACC) Database: The Uniform Data Set
Beekly, D. L., Ramos, E. M., Lee, W. W., Deitrich, W. D., Jacka, M. E., Wu, J., Hubbard, J. L., Koepsell, T. D., Morris, J. C., & Kukull, W. A. (2007) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e318142774e · Cited by 907
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–120 of 120
Towards in vivo PET imaging of primary age-related tauopathy
Therriault, J., & Grothe, M. J. (2023) · Brain · doi:10.1093/brain/awad210 · Cited by 2
CAPS: a simple clinical tool for β-amyloid positivity prediction in clinical Alzheimer syndrome
Lahiri, D., Lima, B. S., Roncero, C., Verhoeff, N. P. L. G., Freedman, M., Al‐Shamaa, S., & Chertkow, H. M. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1422681 · Cited by 2
Azizzadeh, A., Najafi, M., Nafar, Z., Salehzehi, S., Jahromi, S. A., Fallah, H., Ghoshouni, H., & Initiative, A. D. N. (2025) · Neurological Sciences · doi:10.1007/s10072-025-08268-7 · Cited by 2
The biological diagnosis of Alzheimer’s disease using blood-based biomarkers: A Canadian prospective
Kumar, P., Mousavi, A., & Frykman, H. (2025) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2025.110980 · Cited by 2
Singh, R. K., Bekena, S., Damera, N., Zhu, Y., Trani, J., & Babulal, G. M. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251365219 · Cited by 4
Alzheimer dementia with sparse amyloid—AD mimic or variant?
Serrano‐Pozo, A., & Hyman, B. T. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.221 · Cited by 1
Self-citationAlzheimer's Disease: Current Clinical and Neuropathologic Diagnostic Criteria
Ka, J. (2014) · Cited by 1
New Perspectives for Treatment in Alzheimer’s Disease
Loureiro, J. C., Silva, L. F. D. A. L. E., Pais, M. V., & Forlenza, O. V. (2022) · Springer eBooks · doi:10.1007/978-3-030-94383-7_10 · Cited by 1
Assessment of Alzheimer-related Pathologies of Dementia Using Machine Learning Feature SelectionPreprint
Rajab, M. A., Jammeh, E., Taketa, T., Brayne, C., Matthews, F. E., Su, L., Ince, P. G., Wharton, S. B., & Wang, D. Y. Q. (2022) · medRxiv · doi:10.1101/2022.04.28.22274107 · Cited by 1
The Path of Alzheimer’s disease
Jansen, W. J. (2016) · Research Publications (Maastricht University) · doi:10.26481/dis.20161125wj
Tau PET Distributional Pattern in AD Patients with Visuospatial Dysfunction
Sun, X., Nie, B., Zhao, S., Chen, Q., Li, P., Zhang, T., Pan, T., Feng, T., Wang, L., Yin, X., et al. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666191113152434
Effects of anle138b treatment on amyloid-β neurotoxicity
Thomas, C. (2020) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-8233
Ashford, J. W. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734280398.793553881
Liu, M., Huang, C., Huang, S., Chang, H., Hsu, S., Lin, K., Ho, T., Huang, K., Cheng, C., & Chang, C. (2024) · Research Square · doi:10.21203/rs.3.rs-3932300/v1
The biological diagnosis of Alzheimer’s disease using blood-based biomarkers: a Canadian prospective
Kumar, P., Mousavi, A., & Frykman, H. (2025) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2025.111015
Rajab, M. D., Jammeh, E., Taketa, T., Brayne, C., Matthews, F. E., Su, L., Ince, P. G., Wharton, S. B., & Wang, D. (2024) · Figshare · doi:10.6084/m9.figshare.26574064
Ramirez, A., Adami, P. V. M., de Alvarenga, J. C., Freccero, P., Huber, H., Fernandez, J., Burgos, I. C. B., Postillone, M. B., Engelmann, G. T. O., Mintz, I., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-8216169/v1
Neurotoxicité précoce et mécanismes de neuroprotection dans des modèles poisson‐zèbre de tauopathies
Barbereau, C. (2020) · theses.fr (ABES) · doi:10.70675/dfe1802ez70f2z4da6zb3e5z63d1de7a429c
Juni, J. E., Burns, J. M., Salat, D. H., Hill, D., Tally, S., Martin, J. S., Devous, M. D., & Moriarty, P. M. (2026) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/15333175261451918
Vázquez-Villaseñor, I., Benson, B. C., Richardson, C. D., Waller, R., Castelli, L. M., Simpson, J. E., Matthews, F. E., Brayne, C., & Wharton, S. B. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27156964
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
