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

Mattsson, Niklas LU ; Insel, Philip LU ; Palmqvist, Sebastian LU ; Stomrud, Erik LU ; van Westen, Danielle LU ; Minthon, Lennart LU ; Zetterberg, Henrik; Blennow, Kaj and Hansson, Oskar LU (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)
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organization
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type
Contribution to journal
publication status
published
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in
Nature Communications
volume
7
issue
7
publisher
Nature Publishing Group
external identifiers
  • pmid:26948379
  • scopus:84960324758
  • wos:000371720400001
ISSN
2041-1723
DOI
10.1038/ncomms10918
language
English
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yes
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344b6a71-19f1-4eac-8251-f4aa746e1952 (old id 8856060)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26948379?dopt=Abstract
date added to LUP
2016-03-16 15:34:32
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2017-10-29 04:01:26
@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.},
  articleno    = {10918},
  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},
  volume       = {7},
  year         = {2016},
}