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

Niklas Mattsson; Oscar Eriksson; Olof Lindberg; 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

doi:10.1016/j.neurobiolaging.2018.07.003

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

Neurobiol Aging. 2018 Nov:71:81-90. doi: 10.1016/j.neurobiolaging.2018.07.003. Epub 2018 Jul 11.

Authors

Affiliations

¹ Department of Clinical Sciences, Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund/Malmö, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden; Department of Neurology, Skåne University Hospital, Lund, Sweden. Electronic address: [email protected].
² Department of Clinical Sciences, Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund/Malmö, Sweden.
³ Department of Clinical Sciences, Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund/Malmö, Sweden; Department of Psychiatry and Neurochemistry, Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden.
⁴ Clinical Sciences Lund, Medical Radiation Physics, Lund University, Lund, Sweden.
⁵ Department of Clinical Sciences Lund, Lund University, Skane University Hospital, Diagnostic Radiology, Lund, Sweden.
⁶ Department of Clinical Sciences, Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund/Malmö, Sweden; Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
⁷ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁸ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
⁹ Department of Clinical Sciences, Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund/Malmö, Sweden; Department of Neurology, Skåne University Hospital, Lund, Sweden.
¹⁰ Department of Clinical Sciences, Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund/Malmö, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden.
¹¹ Department of Clinical Sciences, Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund/Malmö, Sweden; Memory Clinic, Skåne University Hospital, Malmö, Sweden. Electronic address: [email protected].

PMID: 30107289
DOI: 10.1016/j.neurobiolaging.2018.07.003

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.

Keywords: APOE; Alzheimer's disease; Biomarkers; Cognition; Imaging; Prodromal.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease / cerebrospinal fluid
Alzheimer Disease / diagnosis*
Alzheimer Disease / genetics*
Alzheimer Disease / pathology
Apolipoproteins E / genetics*
Biomarkers / cerebrospinal fluid
Brain / diagnostic imaging
Brain / pathology*
Female
Humans
Male
Positron-Emission Tomography
Prodromal Symptoms
White Matter / diagnostic imaging
White Matter / physiology

Substances

ApoE protein, human
Apolipoproteins E
Biomarkers