Accumulations of insoluble deposits/aggregates are the hallmarks of several neurodegenerative diseases. Deposits involving Abeta and tau proteins in Alzheimer's disease (AD), alpha-synuclein (alpha-syn) in Parkinson's disease (PD), prion protein (PrP) in prion diseases (PrD), TAR DNA-binding protein 43 (TDP-43) in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia-TDP (FTLD-TDP) are well known examples. Evidence suggests that oligomers represent the more toxic species than fibrillar deposits in neurodegenerative conditions, such as AD, PD, and PrD. The number of Abeta deposits, for example, correlates poorly with disease progression, and many researchers consider them to be inert or even protective. Antibodies targeting beta-sheet oligomer conformations are being developed not only to study neurotoxic oligomers, but also for diagnostic and therapeutic purposes.