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

Open Access 01-12-2017 | Research

Preclinical effects of APOE ε4 on cerebrospinal fluid Aβ42 concentrations

Authors: Ronald Lautner, Philip S. Insel, Tobias Skillbäck, Bob Olsson, Mikael Landén, Giovanni B. Frisoni, Sanna-Kaisa Herukka, Harald Hampel, Anders Wallin, Lennart Minthon, Oskar Hansson, Kaj Blennow, Niklas Mattsson, Henrik Zetterberg

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

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Abstract

Background

From earlier studies it is known that the APOE ε2/ε3/ε4 polymorphism modulates the concentrations of cerebrospinal fluid (CSF) beta-amyloid1–42 (Aβ42) in patients with cognitive decline due to Alzheimer’s disease (AD), as well as in cognitively healthy controls. Here, in a large cohort consisting solely of cognitively healthy individuals, we aimed to evaluate how the effect of APOE on CSF Aβ42 varies by age, to understand the association between APOE and the onset of preclinical AD.

Methods

APOE genotype and CSF Aβ42 concentration were determined in a cohort comprising 716 cognitively healthy individuals aged 17–99 from nine different clinical research centers.

Results

CSF concentrations of Aβ42 were lower in APOE ε4 carriers than in noncarriers in a gene dose-dependent manner. The effect of APOE ε4 on CSF Aβ42 was age dependent. The age at which CSF Aβ42 concentrations started to decrease was estimated at 50 years in APOE ε4-negative individuals and 43 years in heterozygous APOE ε4 carriers. Homozygous APOE ε4 carriers showed a steady decline in CSF Aβ42 concentrations with increasing age throughout the examined age span.

Conclusions

People possessing the APOE ε4 allele start to show a decrease in CSF Aβ42 concentration almost a decade before APOE ε4 noncarriers already in early middle age. Homozygous APOE ε4 carriers might deposit Aβ42 throughout the examined age span. These results suggest that there is an APOE ε4-dependent period of early alterations in amyloid homeostasis, when amyloid slowly accumulates, that several years later, together with other downstream pathological events such as tau pathology, translates into cognitive decline.
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Metadata
Title
Preclinical effects of APOE ε4 on cerebrospinal fluid Aβ42 concentrations
Authors
Ronald Lautner
Philip S. Insel
Tobias Skillbäck
Bob Olsson
Mikael Landén
Giovanni B. Frisoni
Sanna-Kaisa Herukka
Harald Hampel
Anders Wallin
Lennart Minthon
Oskar Hansson
Kaj Blennow
Niklas Mattsson
Henrik Zetterberg
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/s13195-017-0313-3

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