CoChat
Sign Up
Cited by 55Alzheimer's disease research and treatmentsNanoparticle-Based Drug DeliveryNeuroinflammation and Neurodegeneration Mechanisms

Multifunctional Superparamagnetic Iron Oxide Nanoparticles Conjugated with Aβ Oligomer-Specific scFv Antibody and Class A Scavenger Receptor Activator Show Early Diagnostic Potentials for Alzheimer’s Disease

Open access
Liu, Xiao-Ge, Zhang, Lun, Lu, Shuai, Liu, Dong-Qun, Zhang, Ling-Xiao, Yu, Xiao-Lin, Liu, Rui-Tian·2020·International Journal of Nanomedicine
DOI 10.2147/ijn.s240953PMC PMC7360423
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Diagnosing AD before symptoms arise will facilitate earlier intervention. The early diagnostic approaches are thus urgently needed. METHODS: The multifunctional nanoparticles W20/XD4-SPIONs were constructed by the conjugation of oligomer-specific scFv antibody W20 and class A scavenger receptor (SR-A) activator XD4 onto superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs' stability and uniformity in size were measured by dynamic light scattering and transmission electron microscopy. The ability of W20/XD4-SPIONs for recognizing Aβ oligomers (AβOs) and promoting AβOs phagocytosis was assessed by immunocytochemistry and flow cytometry analysis. The blood-brain barrier permeability of W20/XD4-SPIONs was determined by a co-culture transwell model. The in vivo probe distribution of W20/XD4-SPIONs in AD mouse brains was detected by magnetic resonance imaging (MRI). RESULTS: W20/XD4-SPIONs, as an AβOs-targeted molecular MRI contrast probe, readily reached pathological AβOs regions in brains and distinguished AD transgenic mice from WT controls. W20/XD4-SPIONs retained the property of XD4 for SR-A activation and significantly promoted microglial phagocytosis of AβOs. Moreover, W20/XD4-SPIONs exhibited the properties of good biocompatibility, high stability and low cytotoxicity. CONCLUSION: Compared with W20-SPIONs or XD4-SPIONs, W20/XD4-SPIONs show the highest efficiency for AβOs-targeting and significantly enhance AβOs uptake by microglia. As a molecular probe, W20/XD4-SPIONs also specifically and sensitively bind to AβOs in AD brains to provide an MRI signal, demonstrating that W20/XD4-SPIONs are promising diagnostic agents for early-stage AD. Due to the beneficial effect of W20 and XD4 on neuropathology, W20/XD4-SPIONs may also have therapeutic potential for AD .

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.2147/ijn.s240953

Cites

Statistics

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • SPION conjugation with specific antibodies (e.g., the oligomer-specific scFv W20) is a prominent trend for early diagnosis and simultaneous activation of phagocytosis by microglia.

    “A prominent trend involves SPION conjugation with specific antibodies (e.g., the oligomer-specific scFv W20) for early diagnosis and simultaneous activation of phagocytosis by microglia [63].”

    From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [63]

    The Introduction describes a W20/XD4-SPION probe intended for early detection, and the Results report MRI signals distinguishing AD mice from controls and enhanced Aβ oligomer uptake by BV-2 microglial cells. But the phagocytosis-promoting component is the added XD4 peptide, not W20 antibody conjugation alone; the paper also does not establish that this approach is a prominent trend. Page numbers are unavailable in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The most common targeting approach is conjugation of Nps with antibodies or their fragments specific to various forms of Aβ.

    “The most common approach is the conjugation of Nps with antibodies or their fragments specific to various forms of Aβ [63,70,71,81].”

    From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [63]

  • A significant portion of studies use MRI with contrast agents based on gadolinium, SPIONs, or manganese ions, reflecting the researchers' desire to create platforms potentially applicable in clinical practice.

    “A significant portion of the studies use MRI with contrast agents based on gadolinium [70,71], SPIONs [58,63,73,83], or manganese ions [72], reflecting the researchers’ desire to create platforms potentially applicable in clinical practice.”

    From Theranostic Nanoplatforms for Alzheimer's Disease: A Critical Analysis of Conceptual Contradictions (2026) · cites this paper as [63]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

No citation lists for this paper

No citation lists for this paper yet — checked again daily.

References 44 · Cited by 55

Research works printed but not linked: 33

  1. [1]Drew L. An age-old story of dementia. Nature. 2018; 559(7715): S2– S3. doi: 10.1038/d41586-018-05718-5 30046085 · DOI
  2. [3]Georganopoulou DG, Chang L, Nam JM, et al. Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer’s disease. Proc Natl Acad Sci U S A. 2005; 102(7): 2273– 2276. doi: 10.1073/pnas.0409336102 15695586 PMC548981 · DOI · Paper page
  3. [4]Toledo JB, Xie SX, Trojanowski JQ, Shaw LM. Longitudinal change in CSF Tau and Abeta biomarkers for up to 48 months in ADNI. Acta Neuropathol. 2013; 126(5): 659– 670. doi: 10.1007/s00401-013-1151-4 23812320 PMC3875373 · DOI · Paper page
  4. [5]Slemmon JR, Meredith J, Guss V, et al. Measurement of Aβ1-42 in cerebrospinal fluid is influenced by matrix effects. J Neurochem. 2012; 120(2): 325– 333. doi: 10.1111/j.1471-4159.2011.07553.x 22023354 · DOI
  5. [6]Fodero-Tavoletti MT, Okamura N, Furumoto S, et al. 18F-THK523: a novel in vivo tau imaging ligand for Alzheimer’s disease. Brain. 2011; 134(Pt 4): 1089– 1100. doi: 10.1093/brain/awr038 21436112 · DOI
  6. [7]Jack CR Jr., Wiste HJ, Vemuri P, et al. Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer’s disease. Brain. 2010; 133(11): 3336– 3348. doi: 10.1093/brain/awq277 20935035 PMC2965425 · DOI · Paper page
  7. [8]Dolgin E. Alzheimer’s disease is getting easier to spot. Nature. 2018; 559(7715): S10– S12. doi: 10.1038/d41586-018-05721-w 30046081 · DOI
  8. [9]Hane FT, Robinson M, Lee BY, Bai O, Leonenko Z, Albert MS. Recent progress in alzheimer’s disease research, Part 3: diagnosis and treatment. J Alzheimer’s Dis. 2017; 57(3): 645– 665. doi: 10.3233/JAD-160907 28269772 PMC5389048 · DOI
  9. [10]Hodson R. Alzheimer’s disease. Nature. 2018; 559(7715): S1. doi: 10.1038/d41586-018-05717-6 30046078 · DOI
  10. [11]Lane CA, Hardy J, Schott JM. Alzheimer’s disease. Eur J Neurol. 2018; 25(1): 59– 70. doi: 10.1111/ene.13439 28872215 · DOI · Paper page
  11. [14]Poon WW, Blurton-Jones M, Tu CH, et al. beta-Amyloid impairs axonal BDNF retrograde trafficking. Neurobiol Aging. 2011; 32(5): 821– 833. doi: 10.1016/j.neurobiolaging.2009.05.012 19540623 PMC3038182 · DOI
  12. [15]Pigino G, Morfini G, Atagi Y, et al. Disruption of fast axonal transport is a pathogenic mechanism for intraneuronal amyloid beta. Proc Natl Acad Sci U S A. 2009; 106(14): 5907– 5912. doi: 10.1073/pnas.0901229106 19321417 PMC2667037 · DOI
  13. [17]Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med. 2016; 8(6): 595– 608. doi: 10.15252/emmm.201606210 27025652 PMC4888851 · DOI · Paper page
  14. [19]Santos LE, Ferreira ST. Crosstalk between endoplasmic reticulum stress and brain inflammation in Alzheimer’s disease. Neuropharmacology. 2018; 136(Pt B): 350– 360. doi: 10.1016/j.neuropharm.2017.11.016 29129774 · DOI
  15. [20]Forloni G, Balducci C. Alzheimer’s disease, oligomers, and inflammation. J Alzheimer’s Dis. 2018; 62(3): 1261– 1276. doi: 10.3233/JAD-170819 29562537 PMC5869993 · DOI
  16. [22]Bateman RJ, Xiong C, Benzinger TL, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med. 2012; 367(9): 795– 804. doi: 10.1056/NEJMoa1202753 22784036 PMC3474597 · DOI · Paper page
  17. [24]Liu XG, Lu S, Liu DQ, et al. ScFv-conjugated superparamagnetic iron oxide nanoparticles for MRI-based diagnosis in transgenic mouse models of Parkinson’s and Huntington’s diseases. Brain Res. 2019; 1707: 141– 153. doi: 10.1016/j.brainres.2018.11.034 30481502 · DOI
  18. [25]Zhang H, Su YJ, Zhou WW, et al. Activated scavenger receptor A promotes glial internalization of abeta. PLoS One. 2014; 9(4): e94197. doi: 10.1371/journal.pone.0094197 24718459 PMC3981768 · DOI
  19. [26]Whitwell JL. Alzheimer’s disease neuroimaging. Curr Opin Neurol. 2018; 31(4): 396– 404. doi: 10.1097/WCO.0000000000000570 29762152 · DOI
  20. [27]Wang X, Zhang J-H, Wang Y-J, et al. Conformation-dependent single-chain variable fragment antibodies specifically recognize beta-amyloid oligomers. FEBS Lett. 2009; 583(3): 579– 584. doi: 10.1016/j.febslet.2008.12.064 19162022 · DOI
  21. [28]Zhang X, Sun XX, Xue D, et al. Conformation-dependent scFv antibodies specifically recognize the oligomers assembled from various amyloids and show colocalization of amyloid fibrils with oligomers in patients with amyloidoses. Biochim Biophys Acta. 2011; 1814(12): 1703– 1712. doi: 10.1016/j.bbapap.2011.09.005 21979582 · DOI
  22. [29]Reiss AB, Arain HA, Stecker MM, Siegart NM, Kasselman LJ. Amyloid toxicity in Alzheimer’s disease. Rev Neurosci. 2018; 29(6): 613– 627. doi: 10.1515/revneuro-2017-0063 29447116 · DOI · Paper page
  23. [32]Salter MW, Stevens B. Microglia emerge as central players in brain disease. Nat Med. 2017; 23(9): 1018– 1027. doi: 10.1038/nm.4397 28886007 · DOI · Paper page
  24. [33]Husemann J, Loike JD, Anankov R, Febbraio M, Silverstein SC. Scavenger receptors in neurobiology and neuropathology: their role on microglia and other cells of the nervous system. Glia. 2002; 40(2): 195– 205. doi: 10.1002/glia.10148 12379907 · DOI
  25. [34]Bamberger ME, Harris ME, McDonald DR, Husemann J, Landreth GE. A cell surface receptor complex for fibrillar beta-amyloid mediates microglial activation. J Neurosci. 2003; 23(7): 2665– 2674. doi: 10.1523/JNEUROSCI.23-07-02665.2003 12684452 PMC6742111 · DOI · Paper page
  26. [35]Alarcon R, Fuenzalida C, Santibanez M, von Bernhardi R. Expression of scavenger receptors in glial cells. Comparing the adhesion of astrocytes and microglia from neonatal rats to surface-bound beta-amyloid. J Biol Chem. 2005; 280(34): 30406– 30415. doi: 10.1074/jbc.M414686200 15987691 · DOI
  27. [36]Stuart LM, Bell SA, Stewart CR, et al. CD36 signals to the actin cytoskeleton and regulates microglial migration via a p130Cas complex. J Biol Chem. 2007; 282(37): 27392– 27401. doi: 10.1074/jbc.M702887200 17623670 · DOI
  28. [37]Wilkinson K, El Khoury J. Microglial scavenger receptors and their roles in the pathogenesis of Alzheimer’s disease. Int J Alzheimers Dis. 2012; 2012: 489456. 22666621 PMC3362056
  29. [38]Canton J, Neculai D, Grinstein S. Scavenger receptors in homeostasis and immunity. Nat Rev Immunol. 2013; 13(9): 621– 634. doi: 10.1038/nri3515 23928573 · DOI · Paper page
  30. [39]Viola KL, Sbarboro J, Sureka R, et al. Towards non-invasive diagnostic imaging of early-stage Alzheimer’s disease. Nat Nanotechnol. 2015; 10(1): 91– 98. doi: 10.1038/nnano.2014.254 25531084 PMC4300856 · DOI
  31. [40]De M, Chou SS, Joshi HM, Dravid VP. Hybrid magnetic nanostructures (MNS) for magnetic resonance imaging applications. Adv Drug Deliv Rev. 2011; 63(14–15): 1282– 1299. doi: 10.1016/j.addr.2011.07.001 21851844 PMC3381436 · DOI
  32. [41]Wei H, Bruns OT, Kaul MG, et al. Exceedingly small iron oxide nanoparticles as positive MRI contrast agents. Proc Natl Acad Sci U S A. 2017; 114(9): 2325– 2330. doi: 10.1073/pnas.1620145114 28193901 PMC5338531 · DOI
  33. [42]Puzzo D. Abeta oligomers: role at the synapse. Aging (Albany NY). 2019; 11(4): 1077– 1078. doi: 10.18632/aging.101818 30738412 PMC6402528 · DOI

Authors
Liu, X.-G., Zhang, L., Lu, S., Liu, D.-Q., Zhang, L.-X., Yu, X.-L., & Liu, R.-T.
Affiliations
Chinese Academy of Sciences (CN)
Corresponding author
Liu, Rui-Tian
ORCID
Venue
International Journal of Nanomedicine
Publisher
Informa UK Limited
Published
2020-07
Volume
Volume 15
Pages
4919-4932
ISSN
  • 1176-9114 (ISSN-L)
  • 1178-2013
DOI
10.2147/ijn.s240953
PMC
PMC7360423
OpenAlex
W3040701715
Cited by
55
References
44
Citations by year
2026: 4 · 2025: 9 · 2024: 9 · 2023: 10 · 2022: 9 · 2021: 13 · 2020: 1
FWCI
4.96
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Nanomedicine (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
  • Institute of Process Engineering, CAS Institutional Repository (submittedVersion)
Funders
National Natural Science Foundation of China (81971610)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, superparamagnetic iron oxide nanoparticles, amyloid-beta oligomers, single-chain antibody, scavenger receptor A, early diagnosis, microglial phagocytosis, blood-brain barrier permeability, transgenic mouse model, nanoparticle biocompatibility
MeSH terms
Multifunctional Nanoparticles, Alzheimer Disease, Animals, Antibody Specificity, Brain, Magnetic Resonance Imaging, Mice, Transgenic, Phagocytosis, Amyloid beta-Peptides, Microglia, Immunoconjugates, Early Diagnosis, Receptors, Scavenger, Mice, Single-Chain Antibodies, Magnetite Nanoparticles

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