Retardation of Aβ42 fibril formation by apolipoprotein A-I and recombinant HDL particles
(2023) In Journal of Biological Chemistry 299(11).- Abstract
The double nucleation mechanism of amyloid β (Aβ) peptide aggregation is retained from buffer to cerebrospinal fluid (CSF) but with reduced rate of all microscopic processes. Here, we used a bottom-up approach to identify retarding factors in CSF. We investigated the Aβ42 fibril formation as a function of time in the absence and presence of apolipoprotein A-I (ApoA-I), recombinant high-density lipoprotein (rHDL) particles, or lipid vesicles. A retardation was observed in the presence of ApoA-I or rHDL particles, most pronounced with ApoA-I, but not with lipid vesicles. Global kinetic analysis implies that rHDL interferes with secondary nucleation. The effect of ApoA-I could best be described as an interference with secondary and to a... (More)
The double nucleation mechanism of amyloid β (Aβ) peptide aggregation is retained from buffer to cerebrospinal fluid (CSF) but with reduced rate of all microscopic processes. Here, we used a bottom-up approach to identify retarding factors in CSF. We investigated the Aβ42 fibril formation as a function of time in the absence and presence of apolipoprotein A-I (ApoA-I), recombinant high-density lipoprotein (rHDL) particles, or lipid vesicles. A retardation was observed in the presence of ApoA-I or rHDL particles, most pronounced with ApoA-I, but not with lipid vesicles. Global kinetic analysis implies that rHDL interferes with secondary nucleation. The effect of ApoA-I could best be described as an interference with secondary and to a smaller extent primary nucleation. Using surface plasmon resonance and microfluidics diffusional sizing analyses, we find that both rHDL and ApoA-I interact with Aβ42 fibrils but not Aβ42 monomer, thus the effect on kinetics seems to involve interference with the catalytic surface for secondary nucleation. The Aβ42 fibrils were imaged using cryogenic-electron microscopy and found to be longer when formed in the presence of ApoA-I or rHDL, compared to formation in buffer. A retarding effect, as observed in CSF, could be replicated using a simpler system, from key components present in CSF but purified from a CSF-free host. However, the effect of CSF is stronger implying the presence of additional retarding factors.
(Less)
- author
- Frankel, Rebecca LU ; Sparr, Emma LU and Linse, Sara LU
- organization
- publishing date
- 2023-11
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- inhibition, neurodegeneration, plaque, suppression
- in
- Journal of Biological Chemistry
- volume
- 299
- issue
- 11
- article number
- 105273
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:37739034
- scopus:85174446137
- ISSN
- 0021-9258
- DOI
- 10.1016/j.jbc.2023.105273
- language
- English
- LU publication?
- yes
- id
- 49fc65e5-e922-48d0-94b5-c01e221784cc
- date added to LUP
- 2023-12-07 14:53:11
- date last changed
- 2024-04-20 09:08:40
@article{49fc65e5-e922-48d0-94b5-c01e221784cc,
abstract = {{<p>The double nucleation mechanism of amyloid β (Aβ) peptide aggregation is retained from buffer to cerebrospinal fluid (CSF) but with reduced rate of all microscopic processes. Here, we used a bottom-up approach to identify retarding factors in CSF. We investigated the Aβ42 fibril formation as a function of time in the absence and presence of apolipoprotein A-I (ApoA-I), recombinant high-density lipoprotein (rHDL) particles, or lipid vesicles. A retardation was observed in the presence of ApoA-I or rHDL particles, most pronounced with ApoA-I, but not with lipid vesicles. Global kinetic analysis implies that rHDL interferes with secondary nucleation. The effect of ApoA-I could best be described as an interference with secondary and to a smaller extent primary nucleation. Using surface plasmon resonance and microfluidics diffusional sizing analyses, we find that both rHDL and ApoA-I interact with Aβ42 fibrils but not Aβ42 monomer, thus the effect on kinetics seems to involve interference with the catalytic surface for secondary nucleation. The Aβ42 fibrils were imaged using cryogenic-electron microscopy and found to be longer when formed in the presence of ApoA-I or rHDL, compared to formation in buffer. A retarding effect, as observed in CSF, could be replicated using a simpler system, from key components present in CSF but purified from a CSF-free host. However, the effect of CSF is stronger implying the presence of additional retarding factors.</p>}},
author = {{Frankel, Rebecca and Sparr, Emma and Linse, Sara}},
issn = {{0021-9258}},
keywords = {{inhibition; neurodegeneration; plaque; suppression}},
language = {{eng}},
number = {{11}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Retardation of Aβ42 fibril formation by apolipoprotein A-I and recombinant HDL particles}},
url = {{http://dx.doi.org/10.1016/j.jbc.2023.105273}},
doi = {{10.1016/j.jbc.2023.105273}},
volume = {{299}},
year = {{2023}},
}