Characteristics of tau oligomers

Abstract

In Alzheimer disease (AD) and other tauopathies, microtubule-associated protein tau becomes hyperphosphorylated, undergoes conformational changes, aggregates, eventually becoming neurofibrillary tangles (NFTs). As accumulating evidence suggests that NFTs themselves may not be toxic, attention is now turning toward the role of intermediate tau oligomers in AD pathophysiology. Sarkosyl extraction is a standard protocol for investigating insoluble tau aggregates in brains. There is a growing consensus that sarkosyl-insoluble tau correlates with the pathological features of tauopathy. While sarkosyl-insoluble tau from tauopathy brains has been well characterized as a pool of filamentous tau, other dimers, multimers, and granules of tau are much less well understood. There are protocols for identifying these tau oligomers. In this mini review, we discuss the characteristics of tau oligomers isolated via different methods and materials.

Keywords: antibody; dimer; oligomers; sarkosyl-insoluble; tau.

Figure 1

Light microscopic images of immunostained brain sections from a non-transgenic mouse, a rTg4510 mouse, and human with AD. Formalin-fixed paraffin sections were stained with TOC1 (1:2500), MC1 (1:1000), and Ab39 (1:250) antibodies by the Dako Universal Autostainer (Dako, Carpinteria, CA, USA). The sections were then counterstained with hematoxylin. TOC1 diffusely stained cytoplasmic regions of neurons (top panels, rTg4510 and AD brains), while MC1 and Ab39 densely stained these neurons (middle and bottom panels, respectively). This difference in staining pattern is due to the specific binding of TOC1 antibody to premature tau aggregates. Scale Bar, 100 μm.