Evidence map›Paper›PMID 22675537›Full record

ArticlePloS one2012

In vivo detection of amyloid-β deposits using heavy chain antibody fragments in a transgenic mouse model for Alzheimer's disease.

Rob J A Nabuurs, Kim S Rutgers, Mick M Welling, Athanasios Metaxas, Maaike E de Backer, Maarten Rotman, Brian J Bacskai, Mark A van Buchem, Silvère M van der Maarel, Louise van der Weerd

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.7field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 39 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Applications of nanobodies in brain diseases.Frontiers in immunology · 2022
    Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. The Diagnostic Potential of Amyloidogenic Proteins.International journal of molecular sciences · 2021
    Review
  10. Article
  11. Review
  12. Nanobodies as non-invasive imaging tools.Immuno-oncology technology · 2020
    Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Selection and characterization of llama single domain antibodies against N-terminal huntingtin.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2015
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Rob J A NabuursDepartment of Radiology, Leiden University Medical Center, Leiden, The Netherlands. R.J.A.Nabuurs@LUMC.nl
Kim S Rutgers
Mick M Welling
Athanasios Metaxas
Maaike E de Backer
Maarten Rotman
Brian J Bacskai
Mark A van Buchem
Silvère M van der Maarel
Louise van der Weerd
Leiden University Medical Center · NLAcademic Medical Center · NLMassachusetts General Hospital · US

Funding

Multiphoton microscopy for in vivo neural imaging.R01EB000768 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI BACSKAI, BRIAN J · 2002 to 2015
$5.0M
A replacement multiphoton microscope for in vivo imaging in rodent models of neurS10RR025645 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI BACSKAI, BRIAN J · 2009 to 2009
$492k
NCRR NIH HHS S10 RR025645NIBIB NIH HHS R01 EB000768
6 · The paper itself

Abstract

This study investigated the in vivo properties of two heavy chain antibody fragments (V(H)H), ni3A and pa2H, to differentially detect vascular or parenchymal amyloid-β deposits characteristic for Alzheimer's disease and cerebral amyloid angiopathy. Blood clearance and biodistribution including brain uptake were assessed by bolus injection of radiolabeled V(H)H in APP/PS1 mice or wildtype littermates. In addition, in vivo specificity for Aβ was examined in more detail with fluorescently labeled V(H)H by circumventing the blood-brain barrier via direct application or intracarotid co-injection with mannitol. All V(H)H showed rapid renal clearance (10-20 min). Twenty-four hours post-injection (99m)Tc-pa2H resulted in a small yet significant higher cerebral uptake in the APP/PS1 animals. No difference in brain uptake were observed for (99m)Tc-ni3A or DTPA((111)In)-pa2H, which lacked additional peptide tags to investigate further clinical applicability. In vivo specificity for Aβ was confirmed for both fluorescently labeled V(H)H, where pa2H remained readily detectable for 24 hours or more after injection. Furthermore, both V(H)H showed affinity for parenchymal and vascular deposits, this in contrast to human tissue, where ni3A specifically targeted only vascular Aβ. Despite a brain uptake that is as yet too low for in vivo imaging, this study provides evidence that V(H)H detect Aβ deposits in vivo, with high selectivity and favorable in vivo characteristics, making them promising tools for further development as diagnostic agents for the distinctive detection of different Aβ deposits.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsAutoradiographyBlood-Brain BarrierDisease Models, AnimalFluorescent Antibody TechniqueHalf-LifeHumansImmunoglobulin FragmentsImmunoglobulin Heavy ChainsMiceMice, TransgenicPlaque, AmyloidProtein BindingSpecies SpecificityAmyloid beta-PeptidesImmunoglobulin FragmentsImmunoglobulin Heavy Chains

Identifiers

PMID22675537
PMCPMC3366949
OpenAlexW2024456670

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.