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Cerebral white matter lesions - associations with Aβ isoforms and amyloid PET.

van Westen, Danielle LU ; Lindqvist, Daniel LU ; Blennow, Kaj; Minthon, Lennart LU ; Nägga, Katarina LU ; Stomrud, Erik LU ; Zetterberg, Henrik and Hansson, Oskar LU (2016) In Scientific Reports 6.
Abstract
Small vessel disease (SVD) and amyloid deposition may promote each other, with a potential association between SVD and altered production or clearance of β-amyloid (Aβ) affecting its cleavage products. We investigated the relationship between SVD, multiple isoforms of Aβ in cerebrospinal fluid (CSF) and cortical Aβ in 831 subjects with cognitive performance ranging from normal to Alzheimer's disease (AD) (the Swedish BioFINDER study). SVD was estimated as white matter lesions (WML) and lacunes. 18F-flutemetamol PET was performed in 321 subjects. Lower CSF levels of Aβ38 and Aβ40 were consistently associated with increased WML in all subgroups, while lower levels of CSF Aβ42 were associated with WML mainly in AD. CSF Aβ38 and Aβ40 were... (More)
Small vessel disease (SVD) and amyloid deposition may promote each other, with a potential association between SVD and altered production or clearance of β-amyloid (Aβ) affecting its cleavage products. We investigated the relationship between SVD, multiple isoforms of Aβ in cerebrospinal fluid (CSF) and cortical Aβ in 831 subjects with cognitive performance ranging from normal to Alzheimer's disease (AD) (the Swedish BioFINDER study). SVD was estimated as white matter lesions (WML) and lacunes. 18F-flutemetamol PET was performed in 321 subjects. Lower CSF levels of Aβ38 and Aβ40 were consistently associated with increased WML in all subgroups, while lower levels of CSF Aβ42 were associated with WML mainly in AD. CSF Aβ38 and Aβ40 were associated with regional WML in all regions, while CSF Aβ42 was associated with temporal WML only. A composite measure of 18F-flutemetamol uptake was not associated with WML, and regional 18F-flutemetamol uptake only with temporal WML. Lacunes were not associated with Aβ isoforms nor 18F-flutemetamol uptake. Our results suggest that WML may be associated with alterations in the production or clearance of Aβ species, particularly of Aβ38 and Aβ40. However, in AD cases, Aβ42 pathology might be associated with WML, especially in the temporal lobe. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
6
publisher
Nature Publishing Group
external identifiers
  • PMID:26856756
  • Scopus:84957812612
  • WOS:000369615500001
ISSN
2045-2322
DOI
10.1038/srep20709
language
English
LU publication?
yes
id
b6aadd1d-a6b0-49a1-96e2-3dac3aec72ce (old id 8826129)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26856756?dopt=Abstract
date added to LUP
2016-03-03 16:13:57
date last changed
2016-12-04 04:40:54
@misc{b6aadd1d-a6b0-49a1-96e2-3dac3aec72ce,
  abstract     = {Small vessel disease (SVD) and amyloid deposition may promote each other, with a potential association between SVD and altered production or clearance of β-amyloid (Aβ) affecting its cleavage products. We investigated the relationship between SVD, multiple isoforms of Aβ in cerebrospinal fluid (CSF) and cortical Aβ in 831 subjects with cognitive performance ranging from normal to Alzheimer's disease (AD) (the Swedish BioFINDER study). SVD was estimated as white matter lesions (WML) and lacunes. 18F-flutemetamol PET was performed in 321 subjects. Lower CSF levels of Aβ38 and Aβ40 were consistently associated with increased WML in all subgroups, while lower levels of CSF Aβ42 were associated with WML mainly in AD. CSF Aβ38 and Aβ40 were associated with regional WML in all regions, while CSF Aβ42 was associated with temporal WML only. A composite measure of 18F-flutemetamol uptake was not associated with WML, and regional 18F-flutemetamol uptake only with temporal WML. Lacunes were not associated with Aβ isoforms nor 18F-flutemetamol uptake. Our results suggest that WML may be associated with alterations in the production or clearance of Aβ species, particularly of Aβ38 and Aβ40. However, in AD cases, Aβ42 pathology might be associated with WML, especially in the temporal lobe.},
  author       = {van Westen, Danielle and Lindqvist, Daniel and Blennow, Kaj and Minthon, Lennart and Nägga, Katarina and Stomrud, Erik and Zetterberg, Henrik and Hansson, Oskar},
  issn         = {2045-2322},
  language     = {eng},
  publisher    = {ARRAY(0xb207020)},
  series       = {Scientific Reports},
  title        = {Cerebral white matter lesions - associations with Aβ isoforms and amyloid PET.},
  url          = {http://dx.doi.org/10.1038/srep20709},
  volume       = {6},
  year         = {2016},
}