. Author manuscript; available in PMC: 2010 Mar 10.

Published in final edited form as: Curr Alzheimer Res. 2008 Jun;5(3):319–341. doi: 10.2174/156720508784533358

Table 1.

Summary of Structural and Biological Characteristics of Pre-Fibrillar Aβ Assemblies

Assembly	Structural characteristics/production	Biological activity
"Activated monomeric conformer" of Aβ	Produced during aggregation of Aβ40 by constant rotary shaking Measured by turbidity assay and HPLC Postulated to be an oxidative or hydrolytic derivative of Aβ [19] [117] The monomeric nature of these conformers is not confirmed unambiguously.	Forms 2–3-fold more complexes with apoE4 than apoE2 or apoE3 [117] Enhances toxicity and apoptotic activity in neurons [19] Inhibits action potential by blocking fast, inward tetrodotoxin-sensitive Na⁺ channels [122]
Cell-derived Aβ oligomers	Predominantly dimers, trimers, and tetramers, produced by CHO cells transfected with mutated or wild-type APP [23] Resistant to SDS denaturation and to cleavage by insulin degrading enzyme [25]	Inhibit LTP in vivo [25] Impair short-term memory in rats [133] Cause dendritic spine loss [138] Affect synaptic structure and function
Aβ-derived diffusible ligands (ADDLs)	Synthetic species formed in the presence of apoJ [144] in F-12 media [142] or in PBS [145] Small globules 3–8 nm in diameter measured by AFM [121] Polydisperse mixtures of 150–1,000 kDa determined by MALLS [70]	Highly neurotoxic [26, 162] Inhibit LTP [26] Bind to neuronal surfaces [53] co-localizing with neuronal proteins at postsynaptic punctate sites [136, 150] and NR1 and NR2B subunits of NMDAR [136, 150] Promote oxidative stress and increased [Ca²⁺]_i [160] Induce τ phosphorylation [145] Induce IL-1β, iNOS, NO and TNF-α in astrocytes [262]
Protofibrils (PF)	Curvilinear fibril-like structures 6–8 nm in diameter and ≤200 nm long by TEM [30]; a periodicity of 20 nm and diameter of 4.3 nm were determined by AFM [112] Rich in β-sheet structure Bind Congo red and Thioflavin T[10]	Increase EPSCs [29], and cause cell death [29, 31] May activate NMDAR in contrast to fibrils which activate non-NMDA glutamate receptors [263]. Patch-clamping using Aβ42 PF induces reversible, Ca²⁺-dependent increase in spontaneous action potentials and membrane depolarizations. Can inhibit the A- and D-type K⁺ currents, but not other outward/inward rectifying K⁺ channels. PF-induced membrane activity increases [Ca²⁺]_i spikes [264]. Aβ40 containing the E22G substitution forms PF faster and in larger quantities than wild-type Aβ in vitro, suggesting that PF may be the main disease-causing agents in carriers of the Arctic mutation [167].
Aβ*56	Extracted from brains of Tg2576 mice and isolated by immunoaffinity and SEC [32]	Concentration correlates with degree of cognitive deficits Cause defects in long-term spatial memory in rats [32]
Amyloid pores	Channel-like structures of synthetic Aβ, having outer diameter of 8–12 nm and inner diameter of 2–2.5 nm, associated with artificial membrane bilayers [18, 37]	Pore- and channel-forming capacity that may lead to membrane leakage and increased [Ca²⁺]_i [18, 37]