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Effects of APOE ε4 on neuroimaging, cerebrospinal fluid biomarkers, and cognition in prodromal Alzheimer's disease.

Journal article
Authors Niklas Mattsson
Oscar Eriksson
Michael Schöll
Björn Lampinen
Markus Nilsson
Philip S Insel
Ronald Lautner
Olof Strandberg
Danielle van Westen
Henrik Zetterberg
Kaj Blennow
Sebastian Palmqvist
Erik Stomrud
Oskar Hansson
Published in Neurobiology of aging
Volume 71
Pages 81-90
ISSN 1558-1497
Publication year 2018
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 81-90
Language en
Links dx.doi.org/10.1016/j.neurobiolaging...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Neurochemistry

Abstract

Apolipoprotein (APOE) ε4 is a major genetic risk factor for Alzheimer's disease (AD), but its importance for the clinical and biological heterogeneity in AD is unclear, particularly at the prodromal stage. We analyzed 151 prodromal AD patients (44 APOE ε4-negative and 107 APOE ε4-positive) from the BioFINDER study. We tested cognition, 18F-flutemetamol β-amyloid (Aβ) positron emission tomography, cerebrospinal fluid biomarkers of Aβ, tau and neurodegeneration, and magnetic resonance imaging of white matter pathology and brain structure. Despite having similar cortical Aβ-load and baseline global cognition (mini mental state examination), APOE ε4-negative prodromal AD had more nonamnestic cognitive impairment, higher cerebrospinal fluid levels of Aβ-peptides and neuronal injury biomarkers, more white matter pathology, more cortical atrophy, and faster decline of mini mental state examination, compared to APOE ε4-positive prodromal AD. The absence of APOE ε4 is associated with an atypical phenotype of prodromal AD. This suggests that APOE ε4 may impact both the diagnostics of AD in early stages and potentially also effects of disease-modifying treatments.

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