Aggregated A beta 1-42 Is Selectively Toxic for Neurons, Whereas Glial Cells Produce Mature Fibrils with Low Toxicity in DrosophilaShow others and affiliations
2018 (English)In: Cell Chemical Biology, ISSN 2451-9456, E-ISSN 2451-9448, Vol. 25, no 5, p. 595-610Article in journal (Refereed) Published
Abstract [en]
The basis for selective vulnerability of certain cell types for misfolded proteins (MPs) in neurodegenerative diseases is largely unknown. This knowledge is crucial for understanding disease progression in relation to MPs spreading in the CNS. We assessed this issue in Drosophila by cell-specific expression of human A beta 1-42 associated with Alzheimers disease. Expression of A beta 1-42 in various neurons resulted in concentration-dependent severe neurodegenerative phenotypes, and intraneuronal ringtangle-like aggregates with immature fibril properties when analyzed by aggregate-specific ligands. Unexpectedly, expression of A beta 1-42 from a pan-glial driver produced a mild phenotype despite massive brain load of A beta 1-42 aggregates, even higher than in the strongest neuronal driver. Glial cells formed more mature fibrous aggregates, morphologically distinct from aggregates found in neurons, and was mainly extracellular. Our findings implicate that A beta 1-42 cytotoxicity is both cell and aggregate morphotype dependent.
Place, publisher, year, edition, pages
Cambridge, United States: Cell Press , 2018. Vol. 25, no 5, p. 595-610
Keywords [en]
Alzheimer's disease, Aβ1-42, Drosophila melanogaster, Gal4/UAS, neurons, glial cells, amyloid polymorphism, cytotoxicity, neurodegeneration
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:liu:diva-148247DOI: 10.1016/j.chembiol.2018.03.006ISI: 000432448700012PubMedID: 29657084Scopus ID: 2-s2.0-85047149608OAI: oai:DiVA.org:liu-148247DiVA, id: diva2:1213404
Note
Funding Agencies|Swedish Brain Foundation; Swedish Research Council; Goran Gustafsson Foundation; King Gustaf V and Queen Victorias Freemasons Foundation; Swedish Alzheimer foundation
2018-06-042018-06-042019-11-08Bibliographically approved