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cross-linked Aβ | Isolated cysteine linked dimers of Aβ that lack significant secondary structure (O'Nuallain and DMW, unpublished) and behave as true dimers on SEC and analytical ultracentrifugation [77]. | Block LTP in vitro [77] and in vivo [165] and impair the memory of learned behaviour (Cleary and DMW, unpublished).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]. |