Skip to main content

Table 1 Water-soluble non-fibrillar Aβ assemblies

From: Alzheimer's disease: synaptic dysfunction and Aβ

Name Physical Characteristics Biological activity
Protofibrils* β-sheet-rich, curvilinear structures of 6-8 nm in diameter and 5-200 nm in length [63, 118]. Under certain circumstances canalso form annular structures [160]. Alter neuronal activity [108], block in vitro LTP [116] cause memory impairment and phosphorylation of tau [117].
ADDLs A mixture of monomer and heterogenous high molecular weight oligomers [120] some of which appear similar to small protofibrils [121]. Block in vitro LTP [64] and cause loss of synapses and [111] at higher concentrations neuronal death [123].
Globulomers Formed in the presence of SDS or fatty acids they are β-sheet-rich and by AFM appear as spheres of 1-5 nm [161] and elute from SEC with a molecular weight consistent for a globular protein of ~100 kDa. Bind to hippocampal neurons, inhibit LTP in vitro [162] and block P/Q Ca2+ currents [163].
Spheroids Spherical structures of 3-20 nm diameter that co-migrate on glycerol gradients with thyroglobulin (669 kDa) [65]. Similar structures have been immunoisolated from human brain [164]. Induce activation of GSK-3β and cell death in cultured neurons [65].
Disulphide cross-linked Aβ Isolated cysteine linked dimers of Aβ that lack significant secondary structure (O'Nuallain and DMW, unpublished) and behave as true dimers on SEC and analytical ultracentrifugation [77]. Block LTP in vitro [77] and in vivo [165] and impair the memory of learned behaviour (Cleary and DMW, unpublished).
Cell-derived SDS-stable low-n oligomers Present in medium from CHO cells expressing human APP and which migrate on SDS-PAGE and SEC with molecular weights consistent for Aβ dimers and trimers [95, 105]. Block LTP in vitro [104] and in vivo [102] and impair the memory of learned behaviour [107].
Aβ56* An Aβ-immunoreactive species isolated from brains of APP transgenic mice in the presence of 0.01% NP-40 and 0.1% SDS and which migrates on SDS-PAGE and SEC with a molecular weight comparable to a globular protein of 56 kDa [86]. Causes impairment of spatial memory [86].
Brain-derived SDS-stable Aβ dimer Extracted from human brain using aqueous buffer and remain in solution following high speed centrifugation. These species migrate on SDS-PAGE as dimers, but elute from SEC as true dimers and high molecular weight species [77] (McDonald et al. Water- and triton-X100 extracted Aβ is specific for Alzheimer-type dementia, submitted). Block LTP in vitro and in vivo and impair the memory of learned behaviour [77].
  1. Besides the forms of Aβ described above a significant number of other Aβ preparations have been studied, but since most of these have not been characterized beyond the use of denaturing electrophoresis or reactivity with certain antibodies they are not dealt with here.
  2. * Protofibrils appear prior to detection of mature amyloid fibrils and thus are considered as pre-fibrillar assemblies.