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Cited by 49Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

A brain proteomic signature of incipient Alzheimer’s disease in young APOE ε4 carriers identifies novel drug targets

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Roberts, Jackson A., Varma, Vijay R., An, Yang, Varma, Sudhir, Candia, Julián, Fantoni, Giovanna, Tiwari, Vinod, Anerillas, Carlos +23 more·2021·Science Advances
DOI 10.1126/sciadv.abi8178PMC PMC8580310
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Abstract

Brain proteins altered in young APOE ε4 carriers are found decades later in Alzheimer’s disease and present novel drug targets.

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  • The iAD signature is a set of proteins highly expressed in young E4 carrier brains but reduced in AD brains.

    “The iAD signature is a set of proteins highly expressed in young E4 carrier brains but reduced in AD brains (Roberts et al., 2021).”

    From APOE4 reshapes the lipid droplet proteome and modulates microglial inflammatory responses (2025) · cites this paper as Roberts et al., 2021

    The Results (Stage 1: Discovery of the incipient AD signature) identify 25 signature proteins and report that nearly all were increased in young APOE ε4 carriers relative to noncarriers and reduced in AD relative to controls. The claim omits exceptions: one protein was reduced in young carriers, and TBP did not show a consistent direction across the two AD cohorts. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

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Authors
Roberts, J. A., Varma, V. R., An, Y., Varma, S., Candia, J., Fantoni, G., Tiwari, V., Anerillas, C., Williamson, A., Saito, A., Loeffler, T., Schilcher, I., Moaddel, R., Khadeer, M., Lovett, J., Tanaka, T., Pletnikova, O., Troncoso, J. C., Bennett, D. A., Albert, M. S., Yu, K., Niu, M., Haroutunian, V., Zhang, B., Peng, J., Croteau, D. L., Resnick, S. M., Gorospe, M., Bohr, V. A., Ferrucci, L., & Thambisetty, M.
Affiliations
  • National Institutes of Health (US)
  • HiThru Analytics, Laurel, MD 20707, USA.
  • Johns Hopkins University (US)
  • QPS (Austria) (AT)
  • Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Rush University Medical Center (US)
  • St. Jude Children's Research Hospital (US)
  • James J. Peters VA Medical Center (US)
  • Icahn School of Medicine at Mount Sinai (US)
Corresponding author
Thambisetty, Madhav
ORCID
Venue
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Published
2021-11-12
Volume
7
Issue
46
Pages
eabi8178-eabi8178
ISSN
2375-2548 (ISSN-L)
DOI
10.1126/sciadv.abi8178
PMC
PMC8580310
OpenAlex
W3214018797
Cited by
49
References
20
Citations by year
2026: 8 · 2025: 8 · 2024: 14 · 2023: 7 · 2022: 12
FWCI
5.05
Type
journal article
Language
en
Open access
Locations
  • Science Advances (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (U01AG046170, R01AG015819, RF1AG057440, P30AG010161, R01AG053987, P30AG066507, P30AG072975)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, APOE ε4 carriers, early Alzheimer's disease, brain proteomics, therapeutic target, STAT3, Src family kinases, YES1, Fyn, transgenic mouse model, human brain tissue

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 ›

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