Reduced protein solubility - cause or consequence in amyloid disease?
Lindberg, Max LU
; Hu, Jing
LU
; Sparr, Emma
LU
and Linse, Sara
LU
(2025)
In QRB Discovery
6.
- Abstract
In this perspective, we ask the question whether the apparently lower solubility of specific proteins in amyloid disease is a cause or consequence of the protein deposition seen in such diseases. We focus on Alzheimer's disease and start by reviewing the experimental evidence of disease-associated reduction in the measured concentration of amyloid β peptide, Aβ42, in cerebrospinal fluid. We propose a series of possible physicochemical explanations for these observations. These include a reduced solubility, a reduced apparent solubility, as well as a long-lived metastable state manifested in healthy individuals as a free concentration of Aβ42 in the solution phase above the solubility limit. For each scenario, we discuss whether it is... (More)
In this perspective, we ask the question whether the apparently lower solubility of specific proteins in amyloid disease is a cause or consequence of the protein deposition seen in such diseases. We focus on Alzheimer's disease and start by reviewing the experimental evidence of disease-associated reduction in the measured concentration of amyloid β peptide, Aβ42, in cerebrospinal fluid. We propose a series of possible physicochemical explanations for these observations. These include a reduced solubility, a reduced apparent solubility, as well as a long-lived metastable state manifested in healthy individuals as a free concentration of Aβ42 in the solution phase above the solubility limit. For each scenario, we discuss whether it is most likely a cause or a consequence of the observed protein deposition in the disease.
(Less)
- author
- Lindberg, Max
LU
; Hu, Jing
LU
; Sparr, Emma
LU
and Linse, Sara
LU
- organization
- publishing date
- 2025-02-17
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer associated amyloids, amyloid complexes, biomolecular systems, chaperones, physical chemistry, protein biophysics
- in
- QRB Discovery
- volume
- 6
- article number
- e8
- publisher
- Cambridge University Press
- external identifiers
-
- scopus:105000786895
- pmid:40070848
- ISSN
- 2633-2892
- DOI
- 10.1017/qrd.2024.12
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2025 The Author(s).
- id
- f5dedf39-38b5-46d5-98c9-192fc22ed3b5
- date added to LUP
- 2025-12-05 14:50:13
- date last changed
- 2025-12-19 16:49:41
@article{f5dedf39-38b5-46d5-98c9-192fc22ed3b5,
abstract = {{<p>In this perspective, we ask the question whether the apparently lower solubility of specific proteins in amyloid disease is a cause or consequence of the protein deposition seen in such diseases. We focus on Alzheimer's disease and start by reviewing the experimental evidence of disease-associated reduction in the measured concentration of amyloid β peptide, Aβ42, in cerebrospinal fluid. We propose a series of possible physicochemical explanations for these observations. These include a reduced solubility, a reduced apparent solubility, as well as a long-lived metastable state manifested in healthy individuals as a free concentration of Aβ42 in the solution phase above the solubility limit. For each scenario, we discuss whether it is most likely a cause or a consequence of the observed protein deposition in the disease.</p>}},
author = {{Lindberg, Max and Hu, Jing and Sparr, Emma and Linse, Sara}},
issn = {{2633-2892}},
keywords = {{Alzheimer associated amyloids; amyloid complexes; biomolecular systems; chaperones; physical chemistry; protein biophysics}},
language = {{eng}},
month = {{02}},
publisher = {{Cambridge University Press}},
series = {{QRB Discovery}},
title = {{Reduced protein solubility - cause or consequence in amyloid disease?}},
url = {{http://dx.doi.org/10.1017/qrd.2024.12}},
doi = {{10.1017/qrd.2024.12}},
volume = {{6}},
year = {{2025}},
}