SwePub
Sök i LIBRIS databas

  Extended search

onr:"swepub:oai:DiVA.org:uu-357268"
 

Search: onr:"swepub:oai:DiVA.org:uu-357268" > Efficient clearence...

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Efficient clearence of A beta protofibrils in A beta PP-transgenic mice treated with a brain-penetrating bifunctional antibody

Syvänen, Stina (author)
Uppsala universitet,Geriatrik
Hultqvist, Greta, 1980- (author)
Uppsala universitet,Institutionen för farmaceutisk biovetenskap
Gustavsson, Tobias (author)
Uppsala universitet,Geriatrik
show more...
Gumucio, Astrid (author)
Uppsala universitet,Geriatrik
Laudon, Hanna (author)
BioArctic AB, Stockholm, Sweden
Söderberg, Linda (author)
BioArctic AB, Stockholm, Sweden
Ingelsson, Martin (author)
Uppsala universitet,Geriatrik
Lannfelt, Lars (author)
Uppsala universitet,Geriatrik,BioArctic AB, Stockholm, Sweden
Sehlin, Dag, 1976- (author)
Uppsala universitet,Geriatrik
show less...
 (creator_code:org_t)
BIOMED CENTRAL LTD, 2018
2018
English.
In: Alzheimer's Research & Therapy. - : BIOMED CENTRAL LTD. - 1758-9193. ; 10
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • Background: Amyloid-beta (A beta) immunotherapy is one of the most promising disease-modifying strategies for Alzheimer's disease (AD) Despite recent progress targeting aggregated forms of A beta, low antibody brain penetrance remains a challenge In the piesent study, we used transferrin receptor (TfR)-mediated transcytosis to facilitate brain uptake of our previously developed A beta protofibril-selective mAb158, with the aim of increasing the efficacy of immunotherapy directed toward soluble A beta protofibills. Methods: A beta protein precursor (A beta PP)-transgenic mice (tg-ArcSwe) were given a single dose of mAb158, modified for TfR-mediated transcytosis (RmAb158-scFvSDB), in companson with an equimolar dose or a tenfold higher dose of unmodified recombinant mAb158 (RmAb158) Soluble A beta protofibrills and total A beta in the brain were measured by enzyme-linked immunosorbent assay (ELISA) Brain distribution of radiolabeled antibodies was visualized by positron emission tomography (PET) and ex vivo autoiadiography. Results: ELISA analysis of Tris-buffered saline brain extracts demonstrated a 40% reduction of soluble A beta protofibrils in both RmAb158-scFv8D3- and high-dose RmAb158-treated mice, whereas there was no A beta protofibril reduction in mice treated with a low dose of RmAb158. Further, ex vivo autoradiography and PET imaging revealed diffeient brain distribution patterns of RmAb158-scFv8D3 and RmAb158, suggesting that these antibodies may affect A beta levels by different mechanisms. Conclusions: With a combination of biochemical and imaging analyses, this study demonstrates that antibodies engineered to be transported across the blood brain barrier can be used to increase the efficacy of A beta immunotherapy. This strategy may allow for decreased antibody doses and thereby reduced side effects and treatment costs.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Geriatrik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Geriatrics (hsv//eng)

Keyword

Alzheimer's disease (AD)
Immunotherapy
Amyloid-beta (A beta)
Oligomers
Protofibrils
Monoclonal antibody
Blood-brain barrier (BBB)
Transferrin receptor (TfR)-mediated transcytosis

Publication and Content Type

ref (subject category)
art (subject category)

Find in a library

To the university's database

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view