Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Increased amyloidogenic APP processing in APOE ɛ4-negative individuals with cerebral β-amyloidosis.

Mattsson, Niklas LU orcid ; Insel, Philip LU ; Palmqvist, Sebastian LU orcid ; Stomrud, Erik LU orcid ; van Westen, Danielle LU orcid ; Minthon, Lennart LU ; Zetterberg, Henrik ; Blennow, Kaj and Hansson, Oskar LU orcid (2016) In Nature Communications 7(7).
Abstract
Increased APP (amyloid precursor protein) processing causes β-amyloid (Aβ) accumulation in autosomal dominant Alzheimer's disease (AD), but it is unclear if it also affects sporadic Aβ accumulation. We tested healthy controls and patients with mild cognitive symptoms (N=331) in the BioFINDER study, using cerebrospinal fluid (CSF) Aβ40 as a surrogate for amyloidogenic APP processing. We find that levels of brain Aβ fibrils (measured by 18F-flutemetamol PET) are independently associated with high CSF Aβ40 (P<0.001) and APOE ɛ4 (P<0.001). The association between CSF Aβ40 and brain Aβ is stronger in APOE ɛ4-negative than in positive people (P=0.0080). The results are similar for CSF Aβ38 and for a combination of CSF Aβ38 and CSF Aβ40. In... (More)
Increased APP (amyloid precursor protein) processing causes β-amyloid (Aβ) accumulation in autosomal dominant Alzheimer's disease (AD), but it is unclear if it also affects sporadic Aβ accumulation. We tested healthy controls and patients with mild cognitive symptoms (N=331) in the BioFINDER study, using cerebrospinal fluid (CSF) Aβ40 as a surrogate for amyloidogenic APP processing. We find that levels of brain Aβ fibrils (measured by 18F-flutemetamol PET) are independently associated with high CSF Aβ40 (P<0.001) and APOE ɛ4 (P<0.001). The association between CSF Aβ40 and brain Aβ is stronger in APOE ɛ4-negative than in positive people (P=0.0080). The results are similar for CSF Aβ38 and for a combination of CSF Aβ38 and CSF Aβ40. In conclusion, sporadic Aβ accumulation may be partly associated with increased amyloidogenic APP production, especially in APOE ɛ4-negative subjects. The risk for sporadic AD may consequently depend on increased Aβ production, in addition to decreased Aβ clearance. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
7
issue
7
article number
10918
publisher
Nature Publishing Group
external identifiers
  • pmid:26948379
  • scopus:84960324758
  • wos:000371720400001
  • pmid:26948379
ISSN
2041-1723
DOI
10.1038/ncomms10918
language
English
LU publication?
yes
id
344b6a71-19f1-4eac-8251-f4aa746e1952 (old id 8856060)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26948379?dopt=Abstract
date added to LUP
2016-04-01 14:27:36
date last changed
2023-11-13 07:48:14
@article{344b6a71-19f1-4eac-8251-f4aa746e1952,
  abstract     = {{Increased APP (amyloid precursor protein) processing causes β-amyloid (Aβ) accumulation in autosomal dominant Alzheimer's disease (AD), but it is unclear if it also affects sporadic Aβ accumulation. We tested healthy controls and patients with mild cognitive symptoms (N=331) in the BioFINDER study, using cerebrospinal fluid (CSF) Aβ40 as a surrogate for amyloidogenic APP processing. We find that levels of brain Aβ fibrils (measured by 18F-flutemetamol PET) are independently associated with high CSF Aβ40 (P&lt;0.001) and APOE ɛ4 (P&lt;0.001). The association between CSF Aβ40 and brain Aβ is stronger in APOE ɛ4-negative than in positive people (P=0.0080). The results are similar for CSF Aβ38 and for a combination of CSF Aβ38 and CSF Aβ40. In conclusion, sporadic Aβ accumulation may be partly associated with increased amyloidogenic APP production, especially in APOE ɛ4-negative subjects. The risk for sporadic AD may consequently depend on increased Aβ production, in addition to decreased Aβ clearance.}},
  author       = {{Mattsson, Niklas and Insel, Philip and Palmqvist, Sebastian and Stomrud, Erik and van Westen, Danielle and Minthon, Lennart and Zetterberg, Henrik and Blennow, Kaj and Hansson, Oskar}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{7}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Increased amyloidogenic APP processing in APOE ɛ4-negative individuals with cerebral β-amyloidosis.}},
  url          = {{http://dx.doi.org/10.1038/ncomms10918}},
  doi          = {{10.1038/ncomms10918}},
  volume       = {{7}},
  year         = {{2016}},
}