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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2017

Open Access 01-12-2017 | Research

The effects of different familial Alzheimer’s disease mutations on APP processing in vivo

Authors: Steinunn Thordardottir, Anne Kinhult Ståhlbom, Ove Almkvist, Håkan Thonberg, Maria Eriksdotter, Henrik Zetterberg, Kaj Blennow, Caroline Graff

Published in: Alzheimer's Research & Therapy | Issue 1/2017

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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.
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Metadata
Title
The effects of different familial Alzheimer’s disease mutations on APP processing in vivo
Authors
Steinunn Thordardottir
Anne Kinhult Ståhlbom
Ove Almkvist
Håkan Thonberg
Maria Eriksdotter
Henrik Zetterberg
Kaj Blennow
Caroline Graff
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2017
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-017-0234-1

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