Aβ*56 is present in brain extracts enriched for extracellular proteins

Amyloid-β (Aβ) oligomers are believed to be important in the pathogenesis of Alzheimer’s disease (AD). Aβ*56 is an Aβ oligomer that has been reported in several lines of transgenic mice modeling AD, including Tg2576, hAPP-J20, 3xTgAD, 5xFAD, and APPTTA. In Tg2576 mice, Aβ*56 appears several months before neuritic plaques and impairs memory when injected into the brains of healthy rodents. Aβ*56 has several distinctive biochemical features: 1) it is soluble in aqueous buffers, 2) it is stable in the ionic detergent sodium dodecyl sulfate (SDS), 3) it has an apparent mass of 56 kDa whether measured by denaturing SDS polyacrylamide gel electrophoresis or non-denaturing size-exclusion chromatography, 4) it binds to A11 conformational antibodies that recognize non-fibrillar oligomeric assemblies, and 5) it contains canonical Aβ(1-40) and/or Aβ(1-42). Here, we show its presence in Tg2576 brain extracts enriched for extracellular proteins and conclude that Aβ*56 is present in the extracellular space.