Table 2.

Definitions of different aggregate species associated with polyQ aggregation

Aggregate Species	Definition
amorphous aggregate	Protein aggregates that do not have a fibrillar morphology but are larger than what is typically classified as an oligomer. Amorphous aggregates often have a granular appearance as assessed by EM or AFM.
amyloid fibril	Filamentous peptide or protein aggregates characterized by thermodynamic stability, high insolubility, and highly ordered cross-β rich structure. They are often comprised of intertwined protofilaments.
annular aggregate	Ring-shaped aggregates that are sometimes further classified as annular protofibrils or annular oligomers in the literature. Ring diameter can vary greatly. Smaller annular aggregates are hypothesized to potentially form pathogenic pores in membranes.
critical nucleus	The specie that directly initiates fibril formation. The critical nucleus may be monomeric or multimeric.
inclusion body	A large (on the order of microns) accumulation of aggregated material (including fibrils and other aggregate species) within a cell. Their large size makes them easily visible by light microscopy.
off pathway aggregate	An aggregate specie that is associated with an aggregation mechanism that does not lead to fibril formation.
oligomer	Small (on the order of 1-15 nm) protein aggregates with a globular morphology. The term oligomer has been used to describe a variety of aggregates ranging from small multimeric species containing 3-10 proteins to larger structures comprised of over 100 proteins. Oligomers are also often sub-categorized. Sub-categories include reference to their composition (i.e. tetramers, dodecamers, etc.) and being on or off pathway to fibril formation.
on pathway aggregate	An aggregate specie that is associated with an aggregation mechanism that leads directly to fibrils.
protofibril	A soluble, short filamentous aggregate that is smaller than a mature fibril and is often considered an intermediate aggregation structure.
protofilament	A single strand that is intertwined to from a mature fibril.