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Solubility and Metastability of the Amyloidogenic Core of Tau

Axell, Emil LU ; Carlsson, Andreas LU ; Lindberg, Max LU orcid ; Bernfur, Katja LU ; Sparr, Emma LU and Linse, Sara LU (2026) In ACS Chemical Neuroscience 17(3). p.592-598
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... (More)

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.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
amyloid solubility, metastability, monomer−fibril equilibrium, protein quantification, solubility limit, tau amyloid core
in
ACS Chemical Neuroscience
volume
17
issue
3
pages
7 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • scopus:105029244769
  • pmid:41576283
ISSN
1948-7193
DOI
10.1021/acschemneuro.5c00784
language
English
LU publication?
yes
id
39e21eb1-d0e8-4d3b-ac6a-76e1ffbd0bf0
date added to LUP
2026-02-18 14:55:24
date last changed
2026-05-14 04:19:11
@article{39e21eb1-d0e8-4d3b-ac6a-76e1ffbd0bf0,
  abstract     = {{<p>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.</p>}},
  author       = {{Axell, Emil and Carlsson, Andreas and Lindberg, Max and Bernfur, Katja and Sparr, Emma and Linse, Sara}},
  issn         = {{1948-7193}},
  keywords     = {{amyloid solubility; metastability; monomer−fibril equilibrium; protein quantification; solubility limit; tau amyloid core}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{592--598}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{ACS Chemical Neuroscience}},
  title        = {{Solubility and Metastability of the Amyloidogenic Core of Tau}},
  url          = {{http://dx.doi.org/10.1021/acschemneuro.5c00784}},
  doi          = {{10.1021/acschemneuro.5c00784}},
  volume       = {{17}},
  year         = {{2026}},
}