Mattsson, N;
Insel, PS;
Palmqvist, S;
Stomrud, E;
van Westen, D;
Minthon, L;
Zetterberg, H;
... Hansson, O; + view all
(2016)
Increased amyloidogenic APP processing in APOE ɛ4-negative individuals with cerebral β-amyloidosis.
Nature Communications
, 7
, Article 109. 10.1038/ncomms10918.
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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 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.
| Type: | Article |
|---|---|
| Title: | Increased amyloidogenic APP processing in APOE ɛ4-negative individuals with cerebral β-amyloidosis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ncomms10918 |
| Publisher version: | https://doi.org/10.1038/ncomms10918 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Alzheimer's disease, Pathogenesis, Peptides |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10073551 |
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