Therapeutic effects of an amyloid beta antibody fragment
November 2017
Universitat Autònoma de Barcelona, Barcelona, Spain(1)
VU University Medical Center, Amsterdam, Netherlands(2)
VU University Medical Center, Amsterdam, Netherlands(2)
Amyloid-beta-induced cytotoxicity is one of the main pathological features of Alzheimer's disease. Immunotherapy against amyloid-beta peptides and/or aggregates has been intensively studied during the last years with certain success. However, little is known about the effects that other molecules involved in the development of the disease have on the therapeutical performance of the anti-amyloid beta antibodies. A recently published study showed an anti-amyloid beta antibody fragment that restored normal values of apolipoprotein E and J and reduced amyloid beta internalization by glial cells. Here, with the use of mimetic peptides of these apolipoproteins, the effect of the therapeutic antibody is tested on amyloid-beta aggregation and cellular uptake by primary human astrocytes. The results show that apolipoprotein E induced conformational changes and interfered with the reduction of astrocytic amyloid-beta uptake induced by the antibody. Meanwhile, apolipoprotein J seemed to induce the formation of protective fibrils in coordination with the antibody and did not interfere with the uptake of amyloid-beta by astrocytes induced by the antibody fragment. Overall, the researchers state that both lipoproteins and the antibody reduce the astrocytic uptake of amyloid-beta, although through different mechanisms, which could reduce astrocyte malfunction and ultimately increase neuronal viability. Therefore, this study opens the door to continue investigating an anti-amyloid beta antibody fragment that could affect different therapeutic targets at the same time.
Effects of an Aβ-antibody fragment on Aβ aggregation and astrocytic uptake are modulated by apolipoprotein E and J mimetic peptides
Sandra Villegas(1), Robert Veerhuis(2)
Added on: 08-19-2021
[1] https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188191[2] https://data.jrc.ec.europa.eu/dataset/a8fd26ef-b113-47ab-92ba-fd2be449c7eb
