Docosahexaenoic acid stabilizes soluble amyloid-β protofibrils and sustains amyloid-β induced neurotoxicity in vitro

Enrichment of diet and culture media with the polyunsaturated fatty acid docosahexaenoic acid has been found to reduce the amyloid burden in mice and lower amyloid-β (Aβ) levels in both mice and cultured cells. However, the direct interaction of polyunsaturated fatty acids, such as docosahexaenoic acid, with Aβ, and their effect on Aβ aggregation has not been explored in detail. Therefore, we have investigated the effect of docosahexaenoic acid, arachidonic acid and the saturated fatty acid arachidic acid on monomer oligomerization into protofibrils and protofibril fibrillization into fibrils in vitro, using size exclusion chromatography. The polyunsaturated fatty acids docosahexaenoic acid and arachidonic acid at micellar concentrations stabilized soluble Aβ42 wild-type protofibrils, thereby hindering their conversion to insoluble fibrils. As a consequence, docosahexaenoic acid sustained amyloid-β-induced toxicity in PC12 cells over time, whereas Aβ without docosahexaenoic acid stabilization resulted in reduced toxicity, as Aβ formed fibrils. Arachidic acid had no effect on Aβ aggregation, and neither of the fatty acids had any protofibril-stabilizing effect on Aβ42 harboring the Arctic mutation (AβE22G). Consequently, AβArctic-induced toxicity could not be sustained using docosahexaenoic acid. These results provide new insights into the toxicity of different Aβ aggregates and how endogenous lipids can affect Aβ aggregation.

Garlind, Anita (författare)
Berglind-Dehlin, FredrikUppsala universitet,Geriatrik (författare)
Karlsson, GöranUppsala universitet,Institutionen för fysikalisk och analytisk kemi(Swepub:uu)gorakarl (författare)
Edwards, KatarinaUppsala universitet,Institutionen för fysikalisk och analytisk kemi(Swepub:uu)kataedwa (författare)
Gellerfors, PärUppsala universitet,Geriatrik (författare)
Ekholm-Pettersson, FridaUppsala universitet,Geriatrik(Swepub:uu)fpe17837 (författare)
Palmblad, Jan (författare)
Lannfelt, LarsUppsala universitet,Institutionen för folkhälso- och vårdvetenskap(Swepub:uu)lalan021 (författare)
Uppsala universitetGeriatrik (creator_code:org_t)

Av författaren/redakt...: Johansson, Ann-S ...; Garlind, Anita; Berglind-Dehlin, ...; Karlsson, Göran; Edwards, Katarin ...; Gellerfors, Pär; visa fler...; Ekholm-Pettersso ...; Palmblad, Jan; Lannfelt, Lars; visa färre...

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