Thordardottir, S;
Stahlbom, AK;
Almkvist, O;
Thonberg, H;
Eriksdotter, M;
Zetterberg, H;
Blennow, K;
(2017)
The effects of different familial Alzheimer's disease mutations on APP processing in vivo.
Alzheimer's Research & Therapy
, 9
, Article 9. 10.1186/s13195-017-0234-1.
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Abstract
BACKGROUND: Disturbed amyloid precursor protein (APP) processing is considered to be central to the pathogenesis of Alzheimer’s disease (AD). The autosomal dominant form of the disease, familial AD (FAD), may serve as a model for the sporadic form of AD. In FAD the diagnosis of AD is reliable and presymptomatic individuals carrying FAD mutations can give valuable insights into the earliest stages of the disease where therapeutic interventions are thought to be the most effective. METHODS:In the current cross-sectional study, products of APP processing (e.g., sAPPα, sAPPβ, Aβ38, Aβ40 and Aβ42) were measured in the cerebrospinal fluid (CSF) of individuals carrying one of three FAD mutations, APPswe (p.KM670/671NL), APParc (p.E693G) and PSEN1 (p.H163Y), as well as in non-mutation carriers from the same families. RESULTS: We observed pathological APP processing in presymptomatic carriers of FAD mutations, with different profiles of APP and Aβ isoforms in the three mutation carrier groups, APPswe (p.KM670/671NL), APParc (p.E693G) and PSEN1 (p.H163Y), except for the well-established decrease in CSF Aβ42 that was found with all mutations. CONCLUSIONS: These findings add to the current evidence that AD pathophysiology differs between disease-causing mutations and can be monitored in the presymptomatic disease stage by CSF analyses. This may also be important from a therapeutic standpoint, by opening a window to monitor effects of disease-modifying drugs on AD pathophysiology.
| Type: | Article |
|---|---|
| Title: | The effects of different familial Alzheimer's disease mutations on APP processing in vivo |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13195-017-0234-1 |
| Publisher version: | http://dx.doi.org/10.1186/s13195-017-0234-1 |
| Language: | English |
| Additional information: | © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| Keywords: | Alzheimer's disease, Amyloid precursor protein, Biomarkers, Cerebrospinal fluid, Genetics, AMYLOID-PRECURSOR PROTEIN, CEREBROSPINAL-FLUID LEVELS, ALPHA-SECRETASE, BIOMARKERS, GENE, DIAGNOSIS, CONSENSUS, PATTERN, PLASMA, ONSET |
| 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-pp.ucl.ac.uk/id/eprint/1550006 |
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