# Solubility and Metastability of the Amyloidogenic Core of Tau

## TL;DR

This study measures the solubility of a key part of the tau protein linked to Alzheimer's disease, helping understand how it forms harmful amyloid structures.

## Contribution

A new method was developed to quantify the solubility of the amyloidogenic core of tau in vitro.

## Key findings

- The solubility of the tau304–380C322S fragment was measured as 6.1 ± 3.5 nM under specific conditions.
- Three independent methods confirmed the equilibrium concentration of free tau monomers.
- The results provide insights into the metastability and fibril formation of amyloidogenic tau.

## Abstract

Intracellular deposits
of neurofibrillary tau tangles
and extracellular
Aβ plaques are closely associated with Alzheimer’s disease.
The mapping of thermodynamic parameters, including solubility limits,
indicates when a protein forms amyloid fibrils or remains in solution.
This reveals the direction of change of the system and may help in
understanding drift and steady states in living systems. Here we have
developed methodology for tau solubility quantification and determined
the solubility of the amyloidogenic core fragment of tau in
vitro. We monitored the concentration of free tau304–380C322S
fragment at 37 °C in phosphate buffer at pH 8.0 using three separate
methods: HPLC-UV, derivatization with ortho-phthalaldehyde and scintillation
counting. The measurements were repeated over time until a stable
value was reached, implying that an equilibrium with fibrils had been
established. The solubility measurements converged on a free monomer
concentration of 6.1 ± 3.5 nM, which represents the solubility
of the fragment under the current experimental conditions.